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Les traitements médicaux de l’hyperplasie bénigne et du cancer de la prostate reposent essentiellement sur l’inhibition de la signalisation androgénique. Bien qu’initialement efficaces, ces traitements sont tôt ou tard confrontés à une résistance thérapeutique. Des données récentes de séquençage d’ARN sur cellules uniques montrent que les cellules luminales survivant à la déprivation androgénique dans ces contextes pathologiques présentent un profil moléculaire semblable à celui de cellules luminales progénitrices, présentes en faible quantité dans un contexte physiologique. Ce profil moléculaire pourrait constituer un hub de résistance à la castration et résulter, en partie, de la reprogrammation des cellules luminales tumorales. L’inhibition thérapeutique de cette plasticité cellulaire constitue une piste prometteuse pour limiter la progression du cancer prostatique.

We aim to evaluate the impact of preoperative thrombocytosis on oncological outcomes in patients with bladder cancer (BC) who undergo radical cystectomy (RC).Retrospective data collection of 1092 patients managed by RC for BC from 2 tertiary-care centers was performed. Elevated platelet count (PLT) was defined as 450 × 10The median follow-up was 50 months (32-64 months). Thrombocytosis was detected in 18.6% of the patients. The 3-year cancer-specific survival (CSS) for patients with normal PLT count was 92% which was higher than those with elevated PLT count (55%, P 0.001). Similar results were found for the 6-year CSS with 82% for the no thrombocytosis group and 27% for the thrombocytosis group. Thrombocytosis was still significantly associated with poor prognosis for overall survival and recurrence-free survival (P 0.001). In the multivariate analysis, CSS was significantly lower in patients with thrombocytosis (HR = 1.71, 95% CI = 1.22-2.39, P = 0.002). Patients with elevated PLT counts were also significantly more likely to receive adjuvant chemotherapy, to have a T stage pT2b (P = 0.024), to have a positive lymph node, to have variant histology and positive resection margins, and to have concomitant carcinoma in situ (CIS) on final pathology (all P 0.001).Preoperative thrombocytosis was valuable for predicting the oncological outcomes of patients undergoing RC for BC.

Upon its mucosal transmission, HIV type 1 (HIV-1) rapidly targets genital antigen-presenting Langerhans cells (LCs), which subsequently transfer infectious virus to CD4 + T cells. We previously described an inhibitory neuroimmune cross talk, whereby calcitonin gene-related peptide (CGRP), a neuropeptide secreted by peripheral pain-sensing nociceptor neurons innervating all mucosal epithelia and associating with LCs, strongly inhibits HIV-1 transfer. As nociceptors secret CGRP following the activation of their Ca 2+ ion channel transient receptor potential vanilloid 1 (TRPV1), and as we reported that LCs secret low levels of CGRP, we investigated whether LCs express functional TRPV1. We found that human LCs expressed mRNA and protein of TRPV1, which was functional and induced Ca 2+ influx following activation with TRPV1 agonists, including capsaicin (CP). The treatment of LCs with TRPV1 agonists also increased CGRP secretion, reaching its anti-HIV-1 inhibitory concentrations. Accordingly, CP pretreatment significantly inhibited LCs-mediated HIV-1 transfer to CD4 + T cells, which was abrogated by both TRPV1 and CGRP receptor antagonists. Like CGRP, CP-induced inhibition of HIV-1 transfer was mediated via increased CCL3 secretion and HIV-1 degradation. CP also inhibited direct CD4 + T cells HIV-1 infection, but in CGRP-independent manners. Finally, pretreatment of inner foreskin tissue explants with CP markedly increased CGRP and CCL3 secretion, and upon subsequent polarized exposure to HIV-1, inhibited an increase in LC–T cell conjugate formation and consequently T cell infection. Our results reveal that TRPV1 activation in human LCs and CD4 + T cells inhibits mucosal HIV-1 infection, via CGRP-dependent/independent mechanisms. Formulations containing TRPV1 agonists, already approved for pain relief, could hence be useful against HIV-1.

Relationship between GPR126 mutation status and standard clinical pathological and biological parameters in bladder cancer

Survival curves of two patients groups according to GPR126 overexpression status in the series of 59 MIBC. x-axes represents the time (months). y-axes represents A : Recurrence-free-survival ; B: Overall survival. p=value is the result of log-rank test.

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This file contains supplementary figures showing prostate tumor kinetics (Fig S1) and histology (Fig S2) for the two mouse models, the validation of regimens (Fig S3 and S4), the effects of diets (Fig S5) and aging (Fig S6) on cancer hallmarks, and the results of cell studies complementary to main Figures 3 and 4.

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The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion. Cancer Res; 71(24); 7649–58. ©2011 AACR.

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Scrotal calcinosis is a rare disorder characterized by multiple papules or nodules of calcification in the scrotal skin. The pathogenesis of this disease is poorly understood. The condition presents as several brown to yellowish asymptomatic nodules on the scrotum. Excision followed by scrotal reconstruction is the treatment of choice. It leaves a good cosmetic result with low chances of recurrence. Newer treatments, such as ablative lasers, have been proposed with very good results. We describe the case of a 28-year-old patient with a history of severe acne treated with oral isotretinoin that presented for scrotal nodules. On laboratory examination, hypercalcemia was found with normal phosphorus, parathyroid hormone, and vitamin D hormone levels. Hypercalcemia was linked to his isotretinoin therapy. Serum calcium concentrations normalized after cessation of isotretinoin and hydration. Because the patient refused surgery, a biopsy of the lesion confirmed the diagnosis of scrotal calcinosis. Then the patient was referred to a cosmetic laser center to treat his condition.

Introduction: To investigate the safety, oncologic, surgical, and functional outcomes of RPP and RRP for localized prostate cancer (Pca), especially focusing on RPP. Materials and methods: From March 2005 to January 2021, we retrospectively reviewed the records of 685 patients undergoing RPP ( n = 320) or RRP ( n = 365) for localized Pca. Surgical and functional outcomes, and complications were compared. Oncological outcomes were also compared using Kaplan-Meier survival analysis. Results: A higher biochemical recurrence rate were noted in RRP than in RPP group (28.8% vs 21.6%, respectively; p = 0.03). A local recurrence was detected in a few numbers of patients (4.4%) with no statistically significant differences by surgical groups ( p = 0.71). No significant differences were observed in the cancer-specific survival and the overall survival according to the surgical approach. Positive surgical margins were similar in the two techniques. In comparison to RRP, patients undergoing RPP have less postoperative pain, decreased transfusion rate, and less catheterization time. Complete continence was achieved in 96.9% of the RPP group at 18 and 24 months versus 91.8% and 92.3% in the RRP group at 18 and 24 months, respectively ( p = 0.005 and p = 0.01, respectively). At 18 months of follow-up, the nerve-sparing technique was performed equally between the two groups, the mean of erectile function domain improved more in RPP than RRP (12.71 vs 10.42 respectively, p Conclusions: RPP showed acceptable oncologic outcomes and excellent functional outcomes when compared to RRP.

Resume Introduction De nombreuses techniques dites mini-invasives ont emerge ces dernieres annees dans le traitement chirurgical de l’obstruction due a l’hyperplasie benigne de la prostate (HBP). L’objectif de cet article etait de faire le point sur leurs evolutions et leurs resultats respectifs. Materiel et methode Une revue coherente de la litterature entre 2013 et 2020 a ete realisee par un panel d’experts nationaux de la chirurgie de l’HBP. Les donnees ont ensuite ete discutees par l’ensemble des co-auteurs afin d’obtenir un consensus vis-a-vis des articles selectionnes et de leur analyse. Un etat des lieux a enfin ete redige pour proposer une vue d’ensemble de ces avancees technologiques et de leur disponibilite en France. Resultats Le traitement de l’obstruction sous-vesicale liee a l’HBP s’est beaucoup diversifie ces 5 dernieres annees. L’inventaire comporte 5 nouvelles technologies permettant aujourd’hui une desobstruction transuretrale non ablative (UROLIFT®, ITIND®), transuretrale ablative (REZUM®), transuretrale ablative avec assistance robotique (AQUABEAM®) ou endovasculaire par embolisation des arteres prostatiques. Seul l’UROLIFT® est consideree comme une technologie etablie dans les dernieres recommandations de l’EAU. Les quatre autres sont en cours d’evaluation et des recommandations europeennes n’ont ete emises uniquement pour deux d’entre eux, l’AQUABEAM® et l’embolisation des arteres prostatiques. Conclusion Ces nouvelles techniques mini-invasives ont pour but d’augmenter les options therapeutiques pour la prise en charge de l’HBP afin de proposer une prise en charge plus adaptee aux souhaits du patient. Certaines se positionnent en alternative au traitement chirurgical, d’autres a la place du traitement medical ou entre le traitement medical et chirurgical. Ces technologies ne sont pas toutes au meme niveau de developpement, d’evaluation et de niveau de preuve mais ont en commun une diffusion restreinte en France, compte tenu notamment de leur cout. Leur utilisation au sein d’etudes validees permettra de positionner leur utilisation ulterieure de facon plus precise.

Ureteroarterial fistula (UAF) is a rare but life-threatening condition because of massive hemorrhage. Risk factors include degenerative vascular diseases, previous vascular surgery, pelvic radiation, chemotherapy, pelvic surgery, and prolonged ureteral stenting. The most common presentation of UAF is massive hematuria with hemorrhagic shock. The diagnosis is always difficult even with angiography. Endovascular repair with stenting and/or coiling is effective and safe. The surgical treatment should be used in recurrent UAF cases. We reported a rare case describing rapid management of a UAF in a patient who presented with hematuria even when we had no diagnosis on the initial CT scan. The patient was in shock. Deployment of a stent graft within the common iliac artery bypassing the UAF was performed. The patient improved rapidly.

Summary Background Whether multiparametric MRI improves the detection of clinically significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial. We aimed to investigate whether using this approach before biopsy would improve detection of clinically significant prostate cancer in biopsy-naive patients. Methods In this prospective, multicentre, paired diagnostic study, done at 16 centres in France, we enrolled patients aged 18–75 years with prostate-specific antigen concentrations of 20 ng/mL or less, and with stage T2c or lower prostate cancer. Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies, with a planned interval of less than 3 months between MRI and biopsies. An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions. In the same patient, another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher (three cores per lesion) using targeted biopsy based on multiparametric MRI findings. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only. The primary outcome was the detection of clinically significant prostate cancer of International Society of Urological Pathology grade group 2 or higher (csPCa-A), analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review, including patients who had protocol deviations. This study is registered with ClinicalTrials.gov, number NCT02485379, and is closed to new participants. Findings Between July 15, 2015, and Aug 11, 2016, we enrolled 275 patients. 24 (9%) were excluded from the analysis. 53 (21%) of 251 analysed patients had negative (Likert ≤2) multiparametric MRI. csPCa-A was detected in 94 (37%) of 251 patients. 13 (14%) of these 94 patients were diagnosed by systematic biopsy only, 19 (20%) by targeted biopsy only, and 62 (66%) by both techniques. Detection of csPCa-A by systematic biopsy (29·9%, 95% CI 24·3–36·0) and targeted biopsy (32·3%, 26·5–38·4) did not differ significantly (p=0·38). csPCa-A would have been missed in 5·2% (95% CI 2·8–8·7) of patients had systematic biopsy not been done, and in 7·6% (4·6–11·6) of patients had targeted biopsy not been done. Four grade 3 post-biopsy adverse events were reported (3 cases of prostatitis, and 1 case of urinary retention with haematuria). Interpretation There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer; however, this detection was improved by combining both techniques and both techniques showed substantial added value. Thus, obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer but does not seem to avoid the need for systematic biopsy. Funding French National Cancer Institute.

This study evaluated the prognostic value of a panel of 29 oncogenes derived from the analysis of The Cancer Genome Atlas (TCGA data) or from the recent literature on bladder tumors on a well-characterized series of muscle-invasive bladder cancer (MIBC) and non-MIBC (NMIBC) samples and tried to identify molecular prognostic markers. Mutations of HRAS, FGFR3, PIK3CA and TERT were found in 2.9%, 27.2%, 14.9% and 76.7% of tumor samples, respectively. Concerning NMIBC, on multivariate analysis, RXRA and FGFR3 levels were associated with recurrence-free survival (RFS) (p = 0.0022 and p = 0.0069) and RXRA level was associated with progression to muscle-invasive disease (p = 0.0068). We identified a 3-gene molecular signature associated with NMIBC prognosis. FGFR3 overexpression was associated with reduced response to Bacillus Calmette–Guerin treatment (p = 0.037). As regards MIBC, on multivariate analysis, ERCC2 overexpression was associated with RFS (p = 0.0011) and E2F3 and EGFR overexpression were associated with overall survival (p = 0.014 and p = 0.035). RT-PCR findings were confirmed by IHC for FGFR3. Genomic alterations in MIBC revealed in TCGA data also concern NMIBC and seem to be associated with prognosis in terms of recurrence and progression. Correcting these alterations by targeted therapies seems a promising pharmacological approach.

Stem and progenitor cells of the adult prostate epithelium have historically been believed to reside mainly or exclusively within the basal cell compartment and to possess basal-like phenotypic characteristics. Within the past decade, evidence of the existence of luminal epithelial cells exhibiting stem/progenitor properties has been obtained by lineage tracing and by functional characterization of sorted luminal-like cells. In 2020, the boom of single-cell transcriptomics led to increasingly exhaustive profiling of putative mouse luminal progenitor cells and, importantly, to the identification of cognate cells in the human prostate. The enrichment of luminal progenitor cells in genetically modified mouse models of prostate inflammation, benign prostate hypertrophy and prostate cancer, and the intrinsic castration tolerance of these cells, suggest their potential role in prostate pathogenesis and in resistance to androgen deprivation therapy. This Review bridges different approaches that have been used in the field to characterize luminal progenitor cells, including the unification of multiple identifiers employed to define these cells (names and markers). It also provides an overview of the intrinsic functional properties of luminal progenitor cells, and addresses their relevance in mouse and human prostate pathophysiology.

Background Aquablation has emerged as a novel ablative therapy combining image guidance and robotics for targeted waterjet adenoma resection. Objective To describe a standardised technique of aquablation in the treatment of benign prostatic obstruction (BPO), and to report the perioperative and 1-yr functional outcomes obtained by multiple surgeons with no previous experience of the technique. Design, setting, and participants Between September 2017 and January 2018, patients referred to three different urological centres for BPO surgical management were prospectively enrolled to undergo an aquablation procedure. Surgical procedure Aquablation was performed using the Aquabeam system (Procept BioRobotics, Redwood Shores, CA, USA) that combines transrectal prostatic image guidance and robotics bespoke tissue resection with a high-pressure saline jet. The surgeon defines the area of treatment, and the resection is executed automatically. Measurements The primary endpoint was the change in total International Prostate Symptom Score (IPSS) score at 6 and 12 mo. Functional outcomes were assessed at 1, 3, 6, and 12 mo with IPSS, International Index of Erectile Function (IIEF)-15, Sexual Health Inventory for Men, and Male Sexual Health Questionnaire questionnaires and uroflowmetry. Results and limitations Thirty patients were enrolled in the study. The median operative time and resection time were 30.5 (24–35) and 4 (3.1–4.9) min, respectively. The median catheterisation time was 43 (23–49) h. The median hospitalisation stay was 2 (2–4) d. The IPSS score improved to 3 (1–6) at the 6 mo, with a mean change of 15.6 points (95% confidence interval 13–18.2). IPSS improvements persisted at month 12. The maximum urinary flow rate improved to 20.4 (17–26) ml/s at 12 mo. The 6-mo rates of Clavien-Dindo grade 2 and 3 events were 13.3%. There were no reports of incontinence or de novo erectile dysfunction. Postoperative de novo ejaculatory dysfunction was observed in 26.7% of patients. Conclusions This clinical registry confirmed that aquablation was feasible, safe, and effective, and provided immediate good functional results and similar outcomes to those of prior studies despite the lack of surgeons’ previous experience with the technique. Patient summary Aquablation is feasible, safe, and reproducible with promising outcomes for treating benign prostatic enlargement.

Resume Objectif Evaluer, en debut d’experience, la morbidite precoce et plus particulierement l’incontinence urinaire apres enucleation endoscopique de prostate au laser Holmium (HoLEP), en preciser la nature, l’evolution et rechercher des facteurs predictifs de survenue. Patients et methode Nous avons realise une etude observationnelle, analytique, retrospective, monocentrique incluant tous les patients operes d’une hypertrophie benigne de prostate (HBP) par HoLEP entre novembre 2015 et janvier 2017. Les donnees ont ete recueillies en pre-, per- et postoperatoire. Le suivi etait de 6 mois. Resultats Cent soixante et onze patients ont ete inclus. 23 patients (14,6 %) ont eu une complication classee selon Clavien-Dindo [4] : 19 (83 %) Clavien 2, 1 (4 %) Clavien 3b et 3 (13 %) Clavien 4. A 1 mois postoperatoire, 64 (42,7 %) patients presentaient une incontinence urinaire dont 55 (86,1 %) uniquement a l’effort. 18 (32,7 %) etaient incontinent urinaire a 6 mois. L’energie delivree en peroperatoire ainsi que l’IIEF5 preoperatoire etaient statiquement associes a la survenue d’une incontinence urinaire d’effort. Il n’a pas ete mis en evidence de lien entre l’apprentissage et la survenue de l’incontinence. Conclusion Le taux important d’incontinence urinaire post HoLEP en debut d’experience implique une reflexion sur la technique utilisee ainsi que sur l’information delivree aux patients en preoperatoire. Niveau de preuve 4.

Numerous pangenomic studies identified protein-coding genes and signaling pathways involved in bladder carcinogenesis. However, noncoding somatic alterations remain unexplored. A recent study revealed a mutational hotspot in intron 6 of GPR126 gene in 2.7% of a large breast cancer series. As GPR126 is highly expressed in bladder tissues, we investigated here the prevalence and the prognostic significance of these mutations in bladder cancer. We analyzed a cohort of 103 bladder cancers including 44 nonmuscle-invasive bladder cancers (NMIBC) and 59 muscle-invasive bladder cancers (MIBC). GPR126 mutations were analyzed by high-resolution melting and Sanger sequencing, and GPR126 expression levels were assessed using real-time quantitative RT-PCR. In NMIBC, somatic GPR126 noncoding mutations occurred in 47.7% of samples and were negatively associated with GPR126 mRNA levels. GPR126 mutations had higher frequencies in nonsmoker patients and were associated with a prior history of NMIBC. GPR126 overexpression was detected in 70.5% of samples. GPR126 mutation and overexpression status were not associated with outcome. In MIBC, somatic GPR126 mutations occurred in 44.1% of samples. Mutations were more frequent in females. GPR126 overexpression was detected in 27.1% of the sample. A trend toward significance was observed between GPR126 overexpression and better outcome. We identified the second most frequent mutational hotspot after TERT promoter (∼70%) in bladder cancer, with a mutation rate of approximately 50%. Implications: The GPR126 intronic mutational hotspot could be a promising clinical biomarker candidate to monitor tumor burden using circulating tumor DNA in bladder cancer.

This study aimed at reporting a head-to-head comparison between water vapor thermal therapy using the Rezūm™ system and prostatic urethral lift using the Urolift™ system in men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH). From December 2017 to November 2019, consecutive patients who underwent Rezūm™ and Urolift™ procedures in two urology centers have been retrospectively considered. Only patients with a prostate size less than 80 mL were included. We used the PSM method to adjust baseline differences between both groups. The co-primary endpoint included the change in International Prostate Symptom Score (IPSS) and IPSS- quality of life (QoL) from baseline to 12 months. A total of 61 (52.1%) and 56 (47.9%) patients underwent Rezum™ and Urolift™ procedures, respectively. After PSM adjustment, 24 patients were included in both groups. No serious adverse events occurred (> Clavien II) in both groups. At 12 months, higher IPSS improvement was observed in the Rezum™ group (median:4 [IQR 3–5]) than in the Urolift™ group (median:8 [IQR 7–12]), without statistical difference (p = 0.08). The improvement in term of QoL at 12 m was similar (p = 0.43). The retreatment rates were 25% (Urolift™) and 8.3% (Rezum™), p = 0.24. Erection and ejaculatory function scores did not change significantly in either treatment group. Results in the full cohort showed that Rezum™ appeared to deliver greater improvements for IPSS and IPSS-QoL (p

Objective To assess the feasibility, safety and precision of organ-based tracking (OBT)-fusion targeted focal microwave ablation (FMA), in patients with low to intermediate risk prostate cancer. Patients and method Ten patients with a visible index tumor of Gleason score ≤3+4, largest diameter Results Median [IQR] age was 64.5 [61–72] years and baseline PSA was 5 [4.3–8.1] ng/mL. Seven (70%) and 3 (30%) patients had a low and intermediate risk cancer, respectively. Median largest tumor axis was of 11 [9.0–15.0] mm. Median duration of procedure was of 82 [44–170] min. No patient reported any pain or rectal bleeding, and all 10 patients were discharged the next day. Seven days after ablation, total necrosis of the index tumor on MRI was obtained in eight (80% [95%CI 55%-100%]) patients. One patient was treated with radical prostatectomy. Re-biopsy at 6 months in the other 9 did not show evidence of cancer in 4 patients. IPSS, IIEF-5 and MSHQ-EjD-SF were not statistically different between baseline and 6 months follow up. Conclusions OBT-fusion targeted FMA was feasible, precise, and safe in patients with low to intermediate risk localized prostate cancer.

Context A considerable number of patients affected by the overactive bladder syndrome (OAB) do not respond to pharmacotherapy and bladder training due to unsatisfactory response or intolerability. Objective To review the available literature assessing therapeutic effect of the available third-line treatment modalities for OAB. Evidence acquisition PubMed, Medline, and Cochrane databases were searched for all studies comparing outcomes of the available third-line treatment modalities for OAB. Evidence synthesis Several minimally invasive surgical procedures are available for patients with refractory OAB. These therapies include intravesical botulinum toxin type A, posterior tibial nerve stimulation, and sacral neuromodulation. Conclusions None of the mentioned therapeutic modalities shows strong superiority over another. If the results of one therapy are not satisfactory, switching to another third-line treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns. All these factors should be taken into consideration before initiation of treatment. Patient summary In the management of drug-resistant overactive bladder syndrome, the different minimally invasive treatments that are available are equal. If the results of one therapy are not satisfactory, switching to another treatment can be attempted. The treatment algorithm is dependent on several factors, including age, comorbidity, patient preference, surgical expertise, and financial concerns.

To evaluate the association between body mass index (BMI) and oncological outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). We retrospectively reviewed 237 consecutive patients treated with RNU for UTUC at our institution between 1990 and 2012. Univariable and multivariable cox regression models investigated the association of BMI with disease recurrence, cancer-specific mortality, and overall mortality. From the 237 patients, 104 (44%) had a BMI

International audience; PURPOSE:To evaluate perioperative cost related to surgical treatments of benign prostatic obstruction (BPO): photoselective vaporization of the prostate (pvp), holmium/thullium laser enucleation (HoLEP/ThuLEP), transurethral resection of the prostate (TURP) and open prostatectomy (OP).MATERIAL AND METHODS:We retrospectively collected data from 237 patients who consecutively underwent a surgical treatment for BPH between January 2012 and June 2013 at nine institutions in France. An economic simulation model was constructed to estimate the cost of hospitalization related to surgical procedure from the hospital perspective and a cost minimization analysis was performed.RESULTS:TURP, OP, HoLEP/ThuLEP and PVP were performed in 99 (42%), 23 (10%), 64 (27%) and 51 (21%) patients, respectively. For men with prostate size

Die transrektale Sonografie mit systematischer Biopsie gilt derzeit als Standard fur die Diagnose eines Prostatakarzinoms. Allerdings ist das Verfahren nicht immer prazise – hochgradige Erkrankungen konnen ubersehen und niedrig maligne Veranderungen ubertherapiert werden. Die Fusionsbiopsie konnte eine Alternative darstellen, aber dazu muss sie zuverlassig reproduzierbar sein. Das haben Mediziner aus den USA gepruft.

Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented these calcium-triggered tumorigenic effects. Expression profiling and in vitro mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+ resulted in an increase in cell proliferation rate, store-operated calcium entry (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR) expression. Notably, administration of the active vitamin D metabolite calcitriol reversed all these effects. Silencing CaSR or TRPC6 expression in calcium-stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results demonstrate the protective effects of vitamin D supplementation in blocking the progression of early-stage prostate lesions induced by a calcium-rich diet. Cancer Res; 77(2); 355–65. ©2016 AACR.

Calcium stones and calculi are observed in numerous human tissues. They are the result of deposition of calcium salts and are due to high local calcium concentrations. Prostatic calculi are usually classified as endogenous or extrinsic stones. Endogenous stones are commonly caused by obstruction of the prostatic ducts around an enlarged prostate resulting from benign prostatic hyperplasia or from chronic inflammation. The latter occurs mainly around the urethra and is generally caused by reflux of urine into the prostate. Calcium concentrations higher than in the plasma at sites of infection may induce the chemotactic response that eventually leads to recruitment of inflammatory cells. The calcium sensing receptor (CaSR) may be crucial for this recruitment as its expression and activity are increased by cytokines such as IL-6 and high extracellular calcium concentrations, respectively. The links between calcium calculi, inflammation, calcium supplementation, and CaSR functions in prostate cancer patients will be discussed in this review.

Promoter mutations of pleckstrin homology domain-containing S1 (PLEKHS1) are frequent in several cancer types. To evaluate the DNA mutations, the mRNA expression and prognostic value of PLEKHS1 was evaluated in bladder cancer. We investigated DNA mutations and mRNA expression of PLEKHS1 in a first series of 154 bladder tumors [71 non-muscle-invasive bladder cancer (NMIBC) and 83 muscle-invasive bladder cancers (MIBC)] from patients who underwent transurethral bladder resection or radical cystectomy between 2001 and 2006, and 20 normal bladder samples. Results were then validated in a second series of 181 bladder tumors (91 NMIBC and 90 MIBC). All patients have signed an informed consent form. DNA mutations were analysed by high-resolution melt analysis and sanger sequencing. The mRNA expression was measured by real-time reverse-transcriptase quantitative PCR. The results of the molecular analysis were compared with survival data. PLEKHS1 mutations occurred in 25.0 and 32.2% of NMIBC and MIBC, respectively in the first series. These results were confirmed in the second series (33.0 and 37.8% of NMIBC and MIBC, respectively). In MIBC, DNA mutations were significantly more frequent with the basal than non-basal phenotype (61.5 vs. 27.1%; P=0.0025). The PLEKHS1 mRNA level was increased in 22.5 and 27.7% of NMIBC and MIBC tumors but was not associated with DNA mutations. In NMIBC, PLEKHS1 mRNA overexpression was significantly associated with progression to muscle-invasive disease (P=0.0069) and remained an independent prognostic factor on multivariate analysis (P=0.034). DNA mutations of PLEKHS1 occurred in one-third of bladder tumors and was frequent in the basal MIBC phenotype. PLEKHS1 mRNA overexpression may be an independent prognostic factor of progression-free survival in NMIBC.

Lower urinary tract symptoms related to benign prostatic obstruction (BPO) are frequent in men aged > 50 years. Based on the use of innovative medical devices, a number of transurethral ablative techniques have recently been developed for the surgical treatment of BPO. In recent years, GreenLight photoselective vaporization of the prostate (PVP) has been considered as a non-inferior alternative to transurethral resection of the prostate. The GreenLight PVP is usually considered as an interesting surgical option for patients treated via oral anticoagulants (OACs) with regard to its haemostatic properties. The aim of this study was to assess the impact of maintaining OAC treatment in patients undergoing PVP. This study is a multicentre, open-label, randomized controlled trial (RCT) designed to show the non-inferiority of PVP surgery in patients with BPO treated with OACs. This study is designed to enrol 386 OAC-treated patients (treated with vitamin K antagonists and direct oral anticoagulants) who are undergoing PVP for BPO. Patients will be randomized (1:1) to either maintain or stop OAC treatment during the perioperative course. The intervention group will maintain OAC treatment until the day before surgery and resume OAC treatment the day after surgery, whereas the control group will stop OAC treatment (with or without low-molecular-weight heparin bridging therapy) according to the anaesthesia guidelines. The primary outcome of interest to be assessed is the 30-day complications rate according to the Clavien-Dindo classification. The secondary endpoint will examine the 30-day rate of haemorrhagic and thrombotic events. This study will provide 80% power to show non-inferiority, defined as not worse than a 10% (non-inferiority margin) inferior change in the proportion of patients with good outcomes (Clavien-Dindo score

Body mass index (BMI) has been associated with worse outcomes in several solid malignancies. We aimed to evaluate the association between BMI and oncological outcomes in patients treated with radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). We retrospectively reviewed 701 consecutive patients treated with RC and pelvic lymphadenectomy for UCB at our institution between 1995 and 2011. Univariable and multivariable Cox regression models investigated the association of BMI with disease recurrence and cancer-specific mortality. BMI was analyzed as both continuous and categorical variable (

Resume Introduction Les enjeux medicoeconomiques de la prise en charge medicamenteuse de l’hypertrophie benigne de la prostate (HBP) prennent une importance croissante du fait du vieillissement de la population et de la multiplication des options therapeutiques, d’ou la necessite d’evaluer le rapport cout–efficacite pour definir les strategies les plus pertinentes economiquement. L’objectif etait de realiser une revue de la litterature des etudes medicoeconomiques sur la prise en charge medicamenteuse de l’HBP. Methode Une revue de la litterature a identifie 43 articles, 9 ont ete selectionnes pour leur pertinence. Resultats En se basant sur des modeles markoviens, on observait que : la bitherapie et les traitements combines (alphabloquants et inhibiteurs de la 5-alpha reductase [5ARI]) semblaient avoir le meilleur rapport cout–efficacite. Venaient ensuite les alphabloquants moins couteux mais exposant a un plus grand risque de progression et de recours a la chirurgie. Venaient ensuite les 5ARI en monotherapie et pour finir la surveillance simple. Conclusion Les modeles markoviens restent des outils imparfaits et les moyens investis dans les soins dependent a la fois du modele economique ou ils sont mis en place et de la valeur que les individus et la societe donnent a l’efficacite des soins.

Resume But Nous avons voulu evaluer l’impact pronostique du sexe feminin sur le devenir oncologique des patients ayant une tumeur de vessie infiltrant le muscle traites par cystectomie totale. Materiel Les donnees de 701 patients traites par cystectomie totale associee a une lymphadenectomie pelvienne pour une tumeur de vessie infiltrant le muscle ont ete collectees. L’impact du genre sur la recidive tumorale, la mortalite specifique et globale ont ete analyses a l’aide de modeles uni- et multivaries de regression de Cox. Resultats Parmi les 701 patients, il y avait 553 hommes (78,9 %) et 148 femmes (21,1 %). Avec un suivi moyen de 45 mois (ecart interquartile 23–73), 163 patients (23,3 %) ont presente une recidive tumorale et 127 (18,1 %) sont decedes du fait de la tumeur de vessie. En analyses multivariees, apres ajustement sur les facteurs pronostiques cliniques et anatomopathologiques classiques (âge, stade tumoral, grade tumoral, presence d’emboles tumoraux, presence de CIS concomitant, statut ganglionnaire), le sexe feminin etait un facteur pronostique independant associe a la survenue d’une recidive tumorale (RR : 1,73 ; IC 95 % 1,22–2,47 ; p = 0,02) et d’une mortalite specifique (RR = 2,50, IC 95 % = 1,71−3,68 ; p Conclusion Le sexe feminin apparait etre un facteur pronostique independant du devenir oncologique des patients apres cystectomie totale. Il semble pertinent de s’y interesser pour proposer a l’avenir des traitements plus adaptes au pronostic de chaque patient et notamment une prise en charge plus agressive des tumeurs survenant chez les femmes. Niveau de preuve 5.