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Background: Gross Hematuria is a relevant cause of admission to the emergency department in the general population and particularly in older adults (≥80 years). This specific urological symptom is often underestimated and usually associated with benign conditions such as urinary infections or poor hydration. Nevertheless, hematuria could lead to severe acute complications or be the first symptom of urological cancers. Methods: We retrospectively analyzed clinical data from 1169 patients aged ≥80 years consecutively admitted to the emergency department for hematuria. The primary endpoint of the study was to identify risk factors for major complications, and the secondary endpoint was to analyze risk factors for urological cancer diagnosis. The median age was 85 years (IQR 82-88 years), and 908 (77%) were males. Among them, 449 (38.4%) had a past medical history of urological neoplasm (kidney, ureter, bladder, prostate, or urethral cancer). Results: Overall, 87 patients (7.4%) had major complications (patient death, septic shock, and admission to the intensive care unit). Worse vital signs at admission, fever, and confusion (p < 0.001, OR 18.0 IC 95% [5.5-58.7]; p = 0.015, OR 2.0 IC 95% [1.1-3.5]; p = <0.001, OR 4.2 IC 95% [1.9-3.5], respectively), as well as lower hemoglobin values and higher Charlson comorbidity index (p < 0.001, OR 0.8 IC 95% [0.7-0.9]), p = 0.002, OR = 1.2 [1.1-1.3]) were independent predictive factors for major complications. The multivariate analysis identified as risk factors for diagnosis of urological cancer older age, male sex and higher comorbidity (OR 1.05 IC95% [1-1.09]; OR 2.19 IC95% [1.42-3.39] and OR 1.11 IC95% [1.2-1.2], respectively); interestingly the presence of indwelling vesical catheter (IVC) (OR 0.44 IC95% [0.24-0.82]) resulted as an independent factor for absence of urological cancers. Conclusions: Hematuria is a frequent symptom in older adults admitted to the emergency department. While this is often associated with benign conditions, there are some risk factors for major complications and for urological cancer that must be taken into account to identify the patients who need further evaluation or prompt hospital admission.
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Inflammation is widely acknowledged as a significant characteristic of cancer, playing a substantial function in both the initiation and advancement of cancers. In this research, we planned to compare pan-immune inflammation markers and other well-known markers (systemic immune inflammation index and neutrophil to lymphocyte ratio) to predict prognosis in individuals treated with radical cystectomy for bladder cancer. METHODS: In this retrospective analysis, we focused on preoperative PIV, systemic immune inflammation index (SII), and neutrophil-lymphocyte ratio (NLR) in 193 individuals managed with radical cystectomy for bladder cancer between January 2016 and November 2022. Multivariable logistic regression assessments were performed to assess the predictive capabilities of PIV, SII, and NLR for infiltration of lymph nodes (N), aggressive tumor stage (pT3/pT4), and any non-organ limited disease at the time of RC. Multivariable Cox regression analyses were conducted to assess the predictive impact of PIV on Relapse-free survival (RFS), Cancer-specific survival (CSS), and Overall survival (OS). RESULTS: Our individuals were divided into high PIV and low PIV cohorts using the optimal cut-off value (340.96 × 109/L) based on receiver operating characteristic curve analysis for relapse-free survival. In multivariable preoperative logistic regression models, only SII and PIV correlated with the infiltration of lymph nodes, aggressive disease, and any non-organ confined disease. In multivariable Cox regression models considering presurgical clinicopathological variables, a higher PIV was associated with diminished RFS (p = 0.017) and OS (p = 0.029). In addition, in multivariable Cox regression models for postoperative outcomes, a high PIV correlated with both RFS (p = 0.034) and OS (p = 0.048). CONCLUSIONS: Our study suggests that PIV and SII are two very similar markers that may serve as independent and significant predictors of aggressive disease and worse survival impacts on individuals undergoing radical cystectomy for bladder neoplasm.
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Prostate cancer remains a prevalent concern worldwide, necessitating continual advancements in treatment modalities. This abstract explores the role of brachytherapy as a viable and effective option in the management of prostate cancer. Brachytherapy involves the implantation of radioactive sources directly into the prostate, providing a localized dose of radiation. n recent studies and clinical trials, brachytherapy has demonstrated promising outcomes, particularly in terms of disease control and patient outcomes. The treatment's ability to deliver a concentrated intraprostatic dose, often in combination with external beam radiotherapy, has shown favorable results. Furthermore, brachytherapy's impact on disease-free survival and its potential in reducing urinary and bowel toxicity have been subjects of investigation. This abstract delves into the technical aspects, patient outcomes, and emerging trends in brachytherapy for prostate cancer. By examining the current literature and research findings, we aim to shed light on the evolving role of brachytherapy in the comprehensive management of prostate cancer, emphasizing its potential as a valuable therapeutic option.
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Curiethérapie , Tumeurs de la prostate , Mâle , Humains , Curiethérapie/méthodes , Urologues , Tumeurs de la prostate/traitement médicamenteux , Dosimétrie en radiothérapieRÉSUMÉ
BACKGROUND: About 30% of Prostate cancer (PCa) patients progress to metastatic PCa that remains largely incurable. This evidence underlines the need for the development of innovative therapies. In this direction, the potential research focus might be on long non-coding RNAs (lncRNAs) like H19, which serve critical biological functions and show significant dysregulation in cancer. Previously, we showed a transcriptional down-regulation of H19 under combined pro-tumoral estrogen and hypoxia treatment in PCa cells that, in turn, induced both E-cadherin and ß4 integrin expression. H19, indeed, acts as transcriptional repressor of cell adhesion molecules affecting the PCa metastatic properties. Here, we investigated the role of H19/cell adhesion molecules circuitry on in vivo PCa experimental tumor growth and metastatic dissemination models. METHODS: H19 was silenced in luciferase-positive PC-3 and 22Rv1 cells and in vitro effect was evaluated by gene expression, proliferation and invasion assays before and after treatment with the histone lysine demethylase inhibitor, GSK-J4. In vivo tumor growth and metastasis dissemination, in the presence or absence of GSK-J4, were analyzed in two models of human tumor in immunodeficient mice by in vivo bioluminescent imaging and immunohistochemistry (IHC) on explanted tissues. Organotypic Slice Cultures (OSCs) from fresh PCa-explant were used as ex vivo model to test GSK-J4 effects. RESULTS: H19 silencing in both PC-3 and 22Rv1 cells increased: i) E-cadherin and ß4 integrin expression as well as proliferation and invasion, ii) in vivo tumor growth, and iii) metastasis formation at bone, lung, and liver. Of note, treatment with GSK-J4 reduced lesions. In parallel, GSK-J4 efficiently induced cell death in PCa-derived OSCs. CONCLUSIONS: Our findings underscore the potential of the H19/cell adhesion molecules circuitry as a targeted approach in PCa treatment. Modulating this interaction has proven effective in inhibiting tumor growth and metastasis, presenting a logical foundation for targeted therapy.
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OBJECTIVES: The aim of this study is to investi-gate the association between the urinary metabolic milieu and kidney stone recurrence with a validated papillary evaluation score (PPLA). MATERIALS AND METHODS: We prospectively enrolled 30 stone for-mers who underwent retrograde intrarenal surgery procedures. Visual inspection of the accessible renal papillae was performed to calculate PPLA score, based on the characterization of ductal plugging, surface pitting, loss of papillary contour and Randall's plaque extension. Stone compositions, 24h urine collections and kidney stone events during follow-up were collected. Relative supersaturation ratios (RSS) for calcium oxalate (CaOx), brushite and uric acid were calculated using EQUIL-2. PPLA score > 3 was deï¬ned as high. RESULTS: Median follow-up period was 11 months (5, 34). PPLA score was inversely correlated with BMI (OR 0.59, 95% CI 0.38, 0.91, p = 0.018), type 2 diabetes (OR 0.04, 95% CI 0.003, 0.58, p = 0.018) and history of recurrent kidney stones (OR 0.17, 95%CI 0.04, 0.75, p = 0.019). The associations between PPLA score, diabetes and BMI were not conï¬rmed after excluding patients with uric acid stones. Higher PPLA score was associated with lower odds of new kidney stone events during follow-up (OR 0.15, 95% CI 0.02, 1.00, p = 0.05). No other signiï¬cant correla-tions were found. CONCLUSIONS: Our results conï¬rm the lack of efï¬cacy of PPLA score in phenotyping patients affected by kidney stone disease or in predicting the risk of stone recurrence. Larger, long-term studies need to be performed to clarify the role of PPLA on the risk of stone recurrence.
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Diabète de type 2 , Calculs rénaux , Humains , Acide urique , Calculs rénaux/chirurgie , Rein , Médulla rénaleRÉSUMÉ
BACKGROUND: Penile duplex Doppler ultrasound in combination with intra-cavernous injection of vasoactive agents (PDDU-ICI) is the most accepted tool for diagnosis of arteriogenic erectile dysfunction (AED), but is invasive, time consuming and at risk of side effects. OBJECTIVES: The purpose of this pilot study is to evaluate the potential of transrectal color Doppler ultrasound (TR-CDU) of the common penile arteries as a non-invasive method for the diagnosis of AED. MATERIALS AND METHODS: A consecutive series of 61 men consulting for erectile dysfunction (ED) and 20 controls underwent TR-CDU examination, aged from 40 to 80 years. Sonographic parameters were correlated with the International Index of Erectile Function, short form (IIEF-5). Sensitivity and specificity were calculated and the areas under the receiver operating characteristic curves (AUC) were compared to evaluate the diagnostic performance. RESULTS: Receiver operating characteristic curve analysis showed no significant results for IIEF-5 score ⩾21 in relation to the Doppler parameters. However, we found a good diagnostic performance for patients with ED grading from moderate to severe at IIEF-5. In this cohort, we found that mean peak systolic velocity >15.8 cm/s predicted IIEF-5 ⩾17 (AUC = 0.73, p = 0.002) with 61.5% sensitivity and 85.7% specificity. Mean end diastolic velocity >1.46 cm/s predicted IIEF-5 ⩾17 (AUC = 0.68, p = 0.02) with 80.7% sensitivity and 52.4% specificity. Mean resistance index ⩽0.72 predicted IIEF-5 ⩾17 (AUC = 0.71, p = 0.004) with 46.2% sensitivity and 95.2% specificity. Mean pulsatility index ⩽1.41 predicted IIEF-5 ⩾17 (AUC = 0.75, p = 0.0005) with 48.5% sensitivity and 95.14% specificity. CONCLUSIONS: TR-CDU proved to be a feasible and non-invasive procedure, easily repeatable and not time consuming, overcoming the limits of PDDU-ICI. Diagnostic accuracy seems to be promising in discriminating patients with normal erectile function or mild dysfunction from those with moderate to severe ED. However, these findings need to be verified in future controlled randomized clinical trials.
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Dysfonctionnement érectile , Humains , Mâle , Artères , Dysfonctionnement érectile/traitement médicamenteux , Pénis/imagerie diagnostique , Pénis/vascularisation , Projets pilotes , Échographie-doppler couleur , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plusRÉSUMÉ
Prostate cancer therapy for locally advanced and metastatic diseases includes androgen deprivation therapy (ADT). Second-generation antiandrogens have a role in castration-resistant prostate cancer. Nevertheless, some patients do not respond to this therapy, and eventually all the patients became resistant. This is due to modifications to intracellular signaling pathways, genomic alteration, cytokines production, metabolic switches, constitutional receptor activation, overexpression of some proteins, and regulation of gene expression. The aim of this review is to define the most important mechanisms that drive this resistance and the newest discoveries in this field, specifically for enzalutamide and abiraterone, with potential implications for future therapeutic targets. Furthermore, apalutamide and darolutamide share some resistance mechanisms with abiraterone and enzalutamide and could be useful in some resistance settings.
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Antagonistes des androgènes , Tumeurs prostatiques résistantes à la castration , Antagonistes des androgènes/usage thérapeutique , Évolution de la maladie , Humains , Mâle , Tumeurs prostatiques résistantes à la castration/traitement médicamenteux , Tumeurs prostatiques résistantes à la castration/anatomopathologieRÉSUMÉ
Laser technology has been used in Urology since the 80s with a lot of different applications in endoscopic and open surgery. With the developments of the technology and the introduction of new active medium and source of laser energy, this technology have become the gold standard not only in stone surgery but even in benign prostate enlargement (BPE) surgical treatment. Regarding urologic oncology, laser energy has now reached an important role in focal therapy and in conservative treatment. The possibility of having better functional outcomes without any relevant impact on oncological results led to an increased use of laser in penile surgery, with a significant mention in urological guidelines for this option. In urothelial cancers as well, both in conservative management of upper tract tumors that in the treatment of non muscle invasive bladder cancer, a clear role of these relatively new source of energy have been demonstrated. Finally, both in prostate that in renal cancer the strategy of focal therapy may take advantage from this precise and fine technology. In this review we analyzed and described the applications of laser energy in urological cancers with a specific focus on penile, urothelial and prostate cancer.
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Thérapie laser , Hyperplasie de la prostate , Tumeurs de la prostate , Urologie , Humains , Thérapie laser/méthodes , Lasers , Mâle , Hyperplasie de la prostate/chirurgie , Tumeurs de la prostate/chirurgie , TechnologieRÉSUMÉ
Prostate cancer is the second most commonly diagnosed cancer in man. Since the first MRI was performed, enormous progress has been made in diagnosis, treatment, and follow up of PCa, mainly due to multiparametric prostatic MRI (mpMRI). Although mpMRI has become the best imaging tool for identifying PCa, some limitations still exist. Prostate imaging with mpMRI is, to date, the best way to locate suspicious lesions to trigger prostate biopsy, plan active surveillance, or definitive treatment. In case of relapse, mpMRI can help detect local disease and provide specific management. It is well known that there is a subset of patients in whom mpMRI fails to depict csPCa. These missed significant cancers demand great attention. Prostate mpMRI quality depends on several factors related to equipment (including equipment vendor, magnet field and gradient strength, coil set used, software and hardware levels, sequence parameter choices), patient (medications, body habitus, motion, metal implants, rectal gas), and most importantly the radiologic interpretation of images (learning curve effects, subjectivity of observations, interobserver variations, and reporting styles). Inter-reader variability represents a huge current limitation of this method. Therefore, mpMRI remains the best imaging tool available to detect PCa, guiding diagnosis, treatment, and follow up while inter-reader variability represents the best limitation. Radiomics can help identifying imaging biomarkers to help radiologist in detecting significant PCa, reducing examination times, and costs.
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Imagerie par résonance magnétique multiparamétrique , Tumeurs de la prostate , Humains , Biopsie guidée par l'image , Imagerie par résonance magnétique , Mâle , Récidive tumorale locale , Tumeurs de la prostate/imagerie diagnostiqueRÉSUMÉ
BACKGROUND: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30%-40% of these patients may develop prostate cancer (PCa) within a 5-year period, often not clinically significant. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis, but it seem not to be the best strategy. METHODS: Objectives-evaluating the natural history of ASAP, stratifying the risk of csPCa after ASAP, identifying predictive factors of PCa after atypical diagnosis. Materials and methods-retrospective single-institutional study on patients undergoing prostate biopsy for suspicious PCa (2005-2016). We evaluated the incidence of overall PCa, intermediate-high risk of PCa and csPCa in case of ASAP, according to D'Amico classification and Epstein modified criteria. RESULTS: Out of 4.567 patients undergoing prostate biopsy, ASAP was detected in 2.6% of cases. All patients with ASAP underwent repeat saturation biopsy within 6 months and PCa was diagnosed in 34.5%. According to D'Amico classification, 26%, 5.9%, and 2.5% had low, intermediate, and high-risk disease, respectively. According modified Epstein criteria, the incidence of csPCa was 12.6%. LRT showed that the overall probability to develop PCa doubled when PSA density (PSAD) moved from values lower than 0.13 ng/ml/cc to class 0.13-0.30 ng/ml/cc, and it tripled when PSAD was higher than 0.30 ng/ml/cc. CONCLUSIONS: The rate of csPCa in patients with an initial diagnosis of ASAP who had repeat biopsy was 12.6%. The overall PCa rate was 34.5%. Among patient undergoing RP, an upgrading from ncsPCa to csPCa was reported in 35% of cases. PSAD is the only predictive factor directly associated to the risk of developing PCa on repeat biopsy. These ï¬ndings suggest that immediate repeat biopsy remains the correct strategy in absence of novel predictor factors and non-invasive diagnostic evaluations.
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Tumeurs de la prostate , Biopsie , Prolifération cellulaire , Humains , Mâle , Tumeurs de la prostate/diagnostic , Tumeurs de la prostate/épidémiologie , Études rétrospectivesRÉSUMÉ
Biopsy proven Gleason score is essential to decide treatment modalities for prostate cancer, either surgical (radical prostatectomy) or non-surgical (active surveillance, watchful waiting, radiation therapy and hormone therapy). Several studies indicated that biopsy proven Gleason score may underestimate Gleason score at radical prostatectomy, hence we aimed to calculate the minimum length of biopsy cores needed to have Gleason score agreement. We evaluated 115 prostate cancer patients who underwent multiparametric magnetic resonance/transperineal ultrasonography fusion biopsy and subsequently, radical prostatectomy. Biopsy proven Gleason score was consistent with Gleason score at subsequent radical prostatectomy in 82.6% of patients, while in 17.4% of patients, Gleason score was higher at radical prostatectomy. Gleason score agreement showed a strong direct association with a ratio > 0.05 between the total volume of biopsies performed in tumor area and the volume of the corresponding tumor at radical prostatectomy. A significant association was also found with a ratio ≥ 0.0034 between the tumor volume in the biopsy and the volume of the corresponding tumor at radical prostatectomy and with a ratio ≥ 0.086 between the tumor volume in the biopsy and the total volume of biopsies performed in the tumor area. These results could be exploited to calculate the minimum length of biopsy cores needed to have a correct Gleason score estimation and therefore be used in fusion targeted biopsies with volume adjustments.
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The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa); however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers. Cell growth and survival, gene profiling, and evaluation of targeted metabolites and metabolic enzymes were assessed. Computational analysis was made considering expression changes occurring in metabolic markers following MALAT1 targeting in cultured OSCs. MALAT1 silencing reduced expression of some metabolic enzymes, including malic enzyme 3, pyruvate dehydrogenase kinases 1 and 3, and choline kinase A. Consequently, PCa metabolism switched toward a glycolytic phenotype characterized by increased lactate production paralleled by growth arrest and cell death. Conversely, the function of mitochondrial succinate dehydrogenase and the expression of oxidative phosphorylation enzymes were markedly reduced. A similar effect was observed in OSCs. Based on this, a predictive algorithm was developed aimed to predict tumor recurrence in a subset of patients. MALAT1 targeting by gapmer delivery restored normal metabolic energy pathway in PCa cells and OSCs.
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INTRODUCTION: Complete ureteral avulsion represents a rare and fearsome complication of ureteroscopy, reported in less than 1% of cases. In literature there are few reports and different options are presented for its treatment. We present a case of a ureteral avulsion managed with ileal ureter replacement. CASE PRESENTATION: A 67-year-old man with a left proximal ureter stone was treated at our department with ureteroscopy. During retrieval of the instrument a complete ureteral avulsion was discovered, with a so-called "scabbard lesion". We decided to proceed with immediate laparotomy and we performed a ileal ureter replacement. CONCLUSION: Ureteral avulsion is a rare complication but must be known as a possible complication in high volume center. There is no standard definition regarding its treatment, and in our experience immediate treatment with ileal ureter replacement proved to be safe and effective without any changes in renal function.
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INTRODUCTION: Describing the surgical and oncological outcome of bladder-preserving ureter reconstruction (BPUR) with segmental ureteral resection after major gynecologic surgery. MATHERIALS AND METHODS: Patients with BPUR admitted at a single institution between March 2012 and July 2018 were retrospectively analyzed. Surgical and oncological data were assessed. RESULTS: Forty-six women with gynecologic tumors involving the ureter were treated with BPUR. R0 resection was achieved in 40/46 patients (86.9%), while pathologic margins were microscopically positive in 6 women (13.1%). Overall, 12 women (26.0%) received radiotherapy before surgery: among them, 8 patients received neoadjuvant chemoradiotherapy. Twenty-six women underwent BPUR during primary surgery, whereas 20 (43.4%) required BPUR upon recurrence. Twenty-six patients (56.2%) were found to have hydronephrosis at pre-operative workup. The psoas bladder hitch was the most common procedure performed for urinary reconstruction (63%) with respect to direct reimplantation (37%). Fourteen patients (14/46 = 30.4%) experienced urological complications. Urinary leakage occurred in 9 patients (19.5%), specifically: 5 uretero-vaginal fistula, 3 uroperitoneum, 1 uretero-enteral fistula. There were 3 cases (6.5%) of hydronephrosis at the side of ureteroneocystostomy and 2 cases (4.3%) of unilateral renal impairment requiring nephrectomy. At multivariate analysis only pre-operative radiotherapy (p = 0.047) and a history of pelvic irradiation (p = 0.025) were independently associated with an increased risk of developing severe urinary complications. CONCLUSIONS: BPUR is feasible in gynecologic cancer with invasion of the urinary tract. However, since a slight increase of post-operative urological complications was observed in the previously irradiated fields, a personalized surgical planning is recommended for these women in the next future.
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Cystotomie/effets indésirables , Tumeurs de l'appareil génital féminin/chirurgie , Récidive tumorale locale/chirurgie , /effets indésirables , Complications postopératoires/étiologie , Uretère/chirurgie , Adulte , Sujet âgé , Chimioradiothérapie adjuvante , Femelle , Tumeurs de l'appareil génital féminin/complications , Tumeurs de l'appareil génital féminin/anatomopathologie , Tumeurs de l'appareil génital féminin/thérapie , Humains , Hydronéphrose/étiologie , Fistule intestinale/étiologie , Adulte d'âge moyen , Traitement néoadjuvant/effets indésirables , Maladie résiduelle , Traitements préservant les organes , Radiothérapie adjuvante/effets indésirables , /méthodes , Facteurs de risque , Résultat thérapeutique , Uretère/anatomopathologie , Vessie urinaire/chirurgie , Fistule urinaire/étiologie , Fistule vaginale/étiologieRÉSUMÉ
BACKGROUND: Circulating tumor cells (CTCs) represent a prerequisite for the formation of metastases. The aim of the study was to identify the role of CTCs as a biological marker of aggressiveness of prostate cancer and verify the expression of molecular markers predictive of response to different therapeutic approaches. METHODS: Prospective, single-arm, non-randomized trial. Twenty-four patients with prostate cancer were enrolled into two groups: group 1 (N.=11) with localized prostate cancer treated with radical prostatectomy; group 2 (N.=13) with metastatic disease. We performed, dosage of blood PSA and testosterone, detection of EGFR, PSMA, PSA and Androgen Receptor (AR) expression on CTC during pre-treatment and follow-up at 1, 3, 9 and 18 months. RESULTS: A total of 65 blood samples were evaluated. In group 1, pre-treatment sampling was negative for the expression of markers on CTC in 90% of the patients while group 2 pre-treatment sampling was positive for the expression of at least one biomarker in seven of 13 patients (54%). After treatment, four patients in group 2 experienced a reduced expression of the markers on CTC, however, in one case there was a new increase of PSA and PSMA at 3 months. One patient had a positivity of AR at 3 months. CONCLUSIONS: The expression of PSA, PSMA, EGFR and AR on CTCs appears to be absent in the pre-treatment samplings in cases of localized prostate cancer. The same markers are hyper-expressed before treatment mostly in metastatic prostate cancer and can relate with early biochemical relapse.
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Marqueurs biologiques/sang , Cellules tumorales circulantes/anatomopathologie , Tumeurs de la prostate/diagnostic , Tumeurs de la prostate/thérapie , Sujet âgé , Sujet âgé de 80 ans ou plus , Récepteurs ErbB/sang , Études de suivi , Humains , Mâle , Adulte d'âge moyen , Grading des tumeurs , Métastase tumorale , Pronostic , Études prospectives , Antigène spécifique de la prostate/sang , Prostatectomie , Tumeurs prostatiques résistantes à la castration , Récepteurs aux androgènes/sang , Testostérone/sang , Résultat thérapeutiqueRÉSUMÉ
Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion molecules' expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR and Western blot. The molecular mechanism was addressed by chromatin immunoprecipitations, overexpression, and silencing assays. PCa cells' metastatic potential was analyzed by in vitro cell-cell adhesion, motility test, and trans-well invasion assay. We found that combined treatment caused a significant H19 down-regulation as compared with hypoxia. In turn, H19 acts as a transcriptional repressor of cell adhesion molecules, as revealed by up-regulation of both ß3 and ß4 integrins and E-cadherin upon H19 silencing or combined treatment. Importantly, H19 down-regulation and ß integrins induction were also observed in treated OSCs. Combined treatment increased both cell motility and invasion of PCa cells. Lastly, reduction of ß integrins and invasion was achieved through epigenetic modulation of H19-dependent transcription. Our study revealed that estrogen and hypoxia transcriptionally regulate, via H19, cell adhesion molecules redirecting metastatic dissemination from EMT to a ß integrin-mediated invasion.
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Régulation de l'expression des gènes tumoraux , Intégrine bêta3/génétique , Intégrine bêta4/génétique , Tumeurs de la prostate/génétique , ARN long non codant/métabolisme , Animaux , Adhérence cellulaire , Lignée cellulaire , Lignée cellulaire tumorale , Oestrogènes/métabolisme , Oestrogènes/pharmacologie , Humains , Hypoxie , Mâle , Tumeurs de la prostate/métabolisme , Tumeurs de la prostate/physiopathologie , Rats , Facteurs de transcription/métabolisme , Transcription génétiqueRÉSUMÉ
The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact. VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. Interaction with mitochondria is mediated via its C-terminal domain. In VPS13A-depleted cells, ER-mitochondria contact sites are decreased, mitochondria are fragmented and mitophagy is decreased. VPS13A also localizes to lipid droplets and affects lipid droplet motility. In VPS13A-depleted mammalian cells lipid droplet numbers are increased. Our data, together with recently published data from others, indicate that VPS13A is required for establishing membrane contact sites between various organelles to enable lipid transfer required for mitochondria and lipid droplet related processes.
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Réticulum endoplasmique/génétique , Gouttelettes lipidiques/métabolisme , Mitochondries/génétique , Protéines du transport vésiculaire/génétique , Réticulum endoplasmique/métabolisme , Endosomes/génétique , Humains , Mitochondries/métabolisme , Membranes mitochondriales/métabolisme , Neuroacanthocytose/génétique , Maladies neurodégénératives/génétique , Domaines protéiques , Protéines du transport vésiculaire/métabolismeRÉSUMÉ
Kidney stones are a common condition with high direct and indirect costs; to date, the optimal urological approach for some particular presentations including non-lower pole kidney stones between 10 and 20 mm of diameter is not clear. A limited number of randomized controlled trials and observational longitudinal studies suggests that ureterorenoscopy (URS) could be superior to shock-wave lithotripsy (SWL) in achieving stone-free rates in this setting; however, such reports are generally weakened by a number of limitations including small sample size and scarce control for confounding. In this issue, Fankhauser et al. [1] report the results of a large observational retrospective study on the comparative efficacy and safety of URS and SWL for the treatment of previously untreated kidney stones.
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OBJECTIVE: To evaluate prospectively midterm outcomes of a new titanium-coated fixed polypropylene sling for male stress urinary incontinence. MATERIALS AND METHODS: From January 2013 to June 2016, 44 consecutive patients with incontinence caused by radical prostatectomy (39) or transurethral resection of prostate (5) underwent transobturator 2-arm titanium-coated sling (TiLOOP Male) implantation with an inside-out, single-incision technique, leaving the bulbourethral muscle in place. Patients have been assessed postoperatively with uroflowmetry, pad count, International Prostate Symptom Score-Short Form, Incontinence Impact Quetionnaire-7, Patient's Global Impression of Improvement, Overactive Bladder questionnaire, International Prostate Symptom Score, and satisfaction (yes or no). Successful outcome included cure (no pad use or 1 dry "security" pad) or improvement (reduction of at least 50% of the pad count). RESULTS: Evaluated patients had mild (11 of 44, 25%), moderate (26 of 44, 59%), or severe (7 of 44, 16%) incontinence. After a median follow-up of 25 months (range 12-55, minimum 12 months), 24 (54.6%) patients were cured and 10 (22.7%) were improved, which was a global success rate of 77.3%. There were 10 (22.7%) failures in the first 6 months. Zero pad rate was 50%. Subjective success (Patient's Global Impression of Improvement very much or much improved) was achieved in 33 (75%) patients. Mean scores of ICIQ-SF, ICIQ-QoL, and IIQ-7 improved to a statistically significant extent. Satisfaction was reported by 33 (75%) patients. Uroflowmetry parameters were unchanged postoperatively, and most of the complications were Clavien-Dindo grade I. Body mass index ≥30 and previous irradiation or high-intensity focused ultrasound were independent predictors of failure. CONCLUSION: TiLOOP Male provided favorable and stable midterm continence outcomes. The inside-out approach was safe, and the tolerability of the sling and the single-incision technique was satisfactory. Patients with obesity and previous irradiation or high-intensity focused ultrasound should be aware of their higher risk of failure.
Sujet(s)
Implantation de prothèse/méthodes , Bandelettes sous-urétrales , Incontinence urinaire d'effort/chirurgie , Sujet âgé , Études de suivi , Humains , Couches pour incontinents , Mâle , Adulte d'âge moyen , Satisfaction des patients , Polypropylènes , Complications postopératoires , Implantation de prothèse/effets indésirables , Indice de gravité de la maladie , Bandelettes sous-urétrales/effets indésirables , Enquêtes et questionnaires , Titane , Résultat thérapeutique , Incontinence urinaire d'effort/physiopathologie , UrodynamiqueRÉSUMÉ
AIMS: The injection of botulinum neurotoxin A (BTA) into the prostate represents a minimally invasive treatment in patients with lower urinary tract symptoms (LUTS) associated to benign prostatic hyperplasia (BPH). We evaluated the effectiveness of BTA in treating patients with BPH unresponsive to combined medical therapy (CMT), using urodynamic investigations. METHODS: This is a randomized, placebo-controlled, double blind trial. Twenty consecutive patients were randomly assigned to receive intraprostatic BTA injection (n = 10) or saline solution (SS) (n = 10). Patients in the intervention group (IG) received 200-300 UI of BTA diluted in 6-8 mL of SS and injected into the transitional zone. Patients in the control group (CG) were treated with SS alone. Primary endpoint was International Prostate Symptom Score (IPSS). Secondary endpoints were: maximum flow rate (Qmax), postvoid residual volume (PVR), maximum cystometric capacity (MCC), bladder outlet obstruction index (BOOI), safety, quality of life (QoL) score, and Patient Reported Outcome (PROs). RESULTS: All patients in the IG reported subjective improvement starting after 1 month. At 3 months of follow-up IPSS, QoL, PVR were reduced by 55,3% (P < 0.01), and 50% (P < 0.01), 80,6%, (P < 0.01), respectively. Qmax was increased by 68% (P < 0.01). MCC increased by 27% (P < 0.01) and BOOI decreased by 54% (P < 0.01). PROs analysis revealed that 90% of patients in the IG reported a subjective symptomatic relief and treatment satisfaction. No local or systemic side effects were observed in any group. CONCLUSIONS: These results indicated that intraprostatic BTA is safe and can improve LUTS and QoL in patients with BPH and unsatisfactory response to CMT.