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Linda Vignozzi,
Mauro Gacci,
Ilaria Cellai,
Raffaella Santi,
Giovanni Corona,
Annamaria Morelli,
Giulia Rastrelli,
Paolo Comeglio,
Arcangelo Sebastanelli,
Elena Maneschi,
Gabriella Nesi,
Cosimo De Nunzio,
Andrea Tubaro,
Edoardo Mannucci, Marco Carini,
Mario Maggi
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ABSTRACT: Metabolic syndrome (MetS) and benign prostate hyperplasia (BPH) are often comorbid. Chronic inflammation, a determinant pathogenic factor for BPH, is a putative link between the two conditions.
In a multi-center cohort of BPH patients (n = 244) who underwent prostatectomy, we evaluated whether MetS is associated with prostatic inflammation in BPH specimens. In addition, we investigated the in vitro inflammatory effects of metabolic insults on human prostatic myofibroblastic cells (hBPH).
Inflammatory infiltrates score (IS) in prostatectomy specimens showed a step-wise association with the number of MetS factors present (P = 0.001). After adjusting for age, reduced HDL cholesterol, and elevated triglycerides were the only factors significantly associated with IS. Increased IS was also significantly associated with hypogonadism. In an age- and testosterone (T)-adjusted model, dyslipidemia was still associated with IS. To investigate whether metabolic factors could directly trigger prostate inflammation, we performed preliminary studies in myofibroblastic hBPH. Among the different factors, oxidized low-density lipoprotein (oxLDL) showed the highest secretion of IL-8 (>10-fold)-a surrogate marker of prostate inflammation-as well as IL-6, and bFGF. Co-treatment with DHT significantly inhibited oxLDL-induced secretion of IL-8, whilst an AR-antagonist, bicalutamide, reversed DHT effects. DHT suppresses oxLDL receptor (LOX-1) expression.
Our data suggest that fats and insulin could have a detrimental effect on prostate health, boosting inflammation, a key pathogenic factor in BPH. Conversely, beneficial effects of DHT in counteracting lipid- and insulin-induced prostatic alterations, suggest that T-via its conversion into DHT-may have unexpected beneficial effects on prostate health. Prostate 73: 789-800, 2013. © 2012 Wiley Periodicals, Inc.
The Prostate 06/2013; 73(8):789-800. · 3.48 Impact Factor
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ABSTRACT: Background. This study aimed to evaluate the safety and efficacy of a sutureless hemostatic control during laparoscopic nephron sparing surgery (LNSS) for the treatment of small renal masses. Methods. Between November 2007 and August 2010, 245 patients underwent nephron sparing surgery. Overall, 100 patients (41%) had LNSS. Hemostasis was controlled either by a knot-tying suture repair (standard-LNSS) or by a sutureless technique (s-LNSS). The s-LNSS was done using a bipolar cauterization of the resection bed, followed by Floseal apposition. Operative and warm ischemia time (WIT), intraoperative blood loss, hospital stay, blood tests, and perioperative complications were recorded. Results. In 32 cases (32%) hemostasis was controlled by the sutureless technique. The s-LNSS was the treatment of choice for small tumors ≤1.5 cm, and it was also used for the treatment of tumors between 1.6 and 2.5 cm, aside from their spatial extension. Indeed, the mean (range; interquartile range) clinical dimension of the tumors in the s-LNSS group was 1.9 (1-3.5; 1.5-2.1) cm. On the contrary, the vast majority of tumors >2.5 cm were treated with standard-LNSS. Mean (range; interquartile range) WIT in the s-LNSS group was 16 (8-22; 12-16) minutes. The mean (range) intraoperative blood loss in the s-LNSS group was 107 cc (25-205). No postoperative early and late bleeding were reported in the s-LNSS group, and the mean (range) time to drainage removal and time to discharge were 3 (2-5) and 4 (3-7) days, respectively. Conclusions. The sutureless technique with bipolar cauterization of the surgical bed and Floseal apposition is safe and effective for the hemostatic control in the treatment of small cortical masses. It can be always used for tumors ≤1.5 cm and can be a valid option also for tumors between 1.6 and 2.5 cm, aside from their spatial extension.
Surgical Innovation 04/2013; · 2.13 Impact Factor
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Mauro Gacci,
Omar Saleh,
Tommaso Cai,
John L Gore,
Carolina D Elia,
Andrea Minervini,
Lorenzo Masieri,
Claudia Giannessi,
Michele Lanciotti,
Virginia Varca,
Alchiede Simonato,
Sergio Serni,
Giorgio Carmignani, Marco Carini
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ABSTRACT: Purpose: Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneousureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months).Materials and methods: All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. RESULTS: We identified 37 females (median age: 68, range 45--82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater -- we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). CONCLUSIONS: In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.
Health and Quality of Life Outcomes 03/2013; 11(1):43. · 2.11 Impact Factor
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Expert Review of Medical Devices 03/2013; 10(2):153-155. · 2.63 Impact Factor
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ABSTRACT: Introduction: The aim of our study was to determine the validity of the updated nomogram [Briganti et al.: Eur Urol 2012;61:480-487] as a prediction tool for pelvic lymph node invasion (LNI) in the current era by using a large multicentric population of men who underwent extended pelvic lymph node dissection (ePLND) at the time of radical prostatectomy (RP) at tertiary referral centers. Patients and Methods: Between 2000 and 2011, 896 consecutive patients underwent RP and ePLND at two tertiary referral centers for clinically localized prostate cancer (PCa). Uni- and multivariable logistic regression models predicting the presence of LNI at ePLND were built in. Covariates consisted of preoperative PSA, clinical stage, primary and secondary biopsy Gleason grade with or without percentage of positive cores. Patients' data were entered into a logistic model formula derived from the original publication of Briganti. The nomogram was assessed by comparing its predicted probability of LNI with the actual presence of LNI. The area under the curve was used to quantify its predictive accuracy. Results: Mean preoperative PSA, clinical and pathological stage, primary and secondary biopsy and pathological Gleason grade, such as mean number of total cores, positive cores and percentage of positive cores differed significantly between LNI-positive and LNI-negative patients (all p < 0.001 except for number of total cores, p = 0.019). The mean number of lymph nodes removed was 14.8, and LNI was found in 101 patients (11.8%). In the univariate analysis the percentage of positive cores was the most accurate predictor of LNI (72%), followed by PSA (69%), primary biopsy Gleason grade (64%), clinical stage (60%), and secondary biopsy Gleason grade (59%). The predictions of the nomogram were virtually perfect when the predicted probability was ≤20%. We tested the performance characteristics of various Briganti nomogram-derived cut-offs (1-14%) for discriminating between patients with and without LNI. In our population, 41.6% of patients were classified below the 5% cut-off proposed in the original Briganti et al. report. In the multivariate analysis these variables remained statistically significant predictors for the presence of lymph node metastases. The predictive accuracy of the full model reached 79%. Conclusions: The updated nomogram predicting LNI in patients with PCa undergoing ePLND has been externally validated, demonstrating excellent accuracy and calibration characteristics and a general applicability for predicting the presence of LNI.
Urologia Internationalis 12/2012; · 0.99 Impact Factor
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Andrea Minervini,
Gianni Vittori,
Matteo Salvi,
Arcangelo Sebastianelli,
Agostino Tuccio,
Giampaolo Siena,
Lorenzo Masieri,
Mauro Gacci,
Alberto Lapini,
Sergio Serni, Marco Carini
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ABSTRACT: PURPOSE: To assess surgical results and morbidity of tumor enucleation (TE), and to evaluate their correlation with PADUA nephrometric score. METHODS: We prospectively gathered data, including accurate analysis of tumor nephrometry, from 244 consecutive patients treated with TE for clinically localized renal cell carcinoma. All surgical results were collected, and perioperative complications were stratified for severity according to Clavien system. Correlation between preoperative variables and surgical results/complications was assessed with uni- and multivariate analysis. RESULTS: Mean (range) tumor size was 3.6 (0.8-10.0) cm, and mean (range) warm ischemia time was 16.8 (5-35) min. Overall, perioperative complications occurred in 45 patients (18.4 %), and of those 8 were medical and 37 were surgical (4 Clavien grade 1, 25 grade 2, and 8 grade 3) complications. Urine leakage rate was 2.0 %. No grade 4/5 complications occurred in this series. At univariate analysis PADUA score, endophytic tumor growth, tumor diameter, involvement of UCS and renal sinus resulted associated with warm ischemia time (p < 0.0001 each) and surgical complications (p = 0.0007, p = 0.049, p = 0.021, p = 0.036, and p = 0.029, respectively). At logistic regression, nephrometry score resulted independently associated with overall complications (related risk for each increased point 1.54; p = 0.017), surgical complications (related risk 1.58; p = 0.016), and Clavien grade 3 surgical complications (related risk 2.99; p = 0.008). CONCLUSIONS: The TE technique was associated with a 15.2 % surgical complication rate with a 3.3 % reintervention rate (including ureteral stenting and superselective renal artery embolization). Tumor nephrometry and surgical indication resulted independent predictors of Clavien grade 3 complications. The PADUA score is a reliable tool to predict surgical results and morbidity of TE.
Annals of Surgical Oncology 12/2012; · 4.17 Impact Factor
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Beatrice Detti,
Silvia Scoccianti,
Davide Franceschini,
Samantha Cipressi,
Sara Cassani,
Donata Villari,
Mauro Gacci,
Alberto Pupi,
Luca Vaggelli,
Calogero Saieva,
Maurizio Pertici,
Lorenzo Livi,
M Ceroti,
Giulio Nicita, Marco Carini,
Giampaolo Biti
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ABSTRACT: AIM: The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA. MATERIALS AND METHODS: We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT. RESULTS: A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p < 0.0001) and at the multivariate analysis (p < 0.0001). CONCLUSIONS: Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.
Journal of Cancer Research and Clinical Oncology 11/2012; · 2.56 Impact Factor
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Beatrice Detti,
Silvia Scoccianti,
Sara Cassani,
Samantha Cipressi,
Donata Villari,
Alberto Lapini,
Calogero Saieva,
Tommaso Cai,
Maurizio Pertici,
Irene Giacomelli,
Lorenzo Livi,
Marco Ceroti,
Giulio Nicita, Marco Carini,
Giampaolo Biti
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ABSTRACT: AIM: In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART). MATERIALS AND METHODS: Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. RESULTS: In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. CONCLUSION: Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.
Journal of Cancer Research and Clinical Oncology 09/2012; · 2.56 Impact Factor
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ABSTRACT: To investigate the potential role of tumor enucleation (TE) for the treatment of giant angiomyolipomas (AML).
We retrospectively analyzed a prospectively derived database of 707 patients with kidney tumor, who were treated with conservative surgery, between January 1995 and September 2009. Overall, 31 patients had a histopathologic diagnosis of renal AML and of those, 3 patients had a diagnosis of unilateral or bilateral renal mass, with at least one clinically suggestive of giant AML (maximal tumor diameter > or = 9 cm), either central or perihilar. These patients were the subjects of the analysis. Nephron sparing surgery (NSS) was performed as tumor enucleation (TE), carried out by a blunt dissection, using the natural cleavage plane between the tumor and the normal parenchyma.
Preoperative tumor size ranged between 9.0 and 15.0 centimetres. At surgery, after kidney capsule incision, TE was done in all cases. In critical surgical steps, in case of difficult visualization of the correct enucleation plane, a sharp dissection a few millimetres away from the tumor was adopted. Warm ischemia time (WIT) was always below 20 minutes. Intraoperative blood loss was negligible. Unsignificant postoperative creatinine variation was recorded in all cases. No intra- and post-operative complications occurred. At last follow up visit, no tumor recurrence at the enucleation site was reported.
TE technique can be considered a viable and effective treatment option for this very rare pathologic condition, since it provides a maximal glomerular preservation and minimizes WIT and intra- and postoperative complications.
Archivio italiano di urologia, andrologia: organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia 09/2012; 84(3):146-50.
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Paolo Gontero,
Maxine Sun,
Alessandro Antonelli,
Roberto Bertini, Marco Carini,
Giorgio Carmignani,
Nicola Longo,
Giuseppe Martorana,
Andrea Minervini,
Vincenzo Mirone,
Giuseppe Morgia,
Giacomo Novara,
Marco Oderda,
Claudio Simeone,
Alchiede Simonato,
Salvatore Siracusano,
Alessandro Tizzani,
Alessandro Volpe,
Pierre Karakiewicz,
Vincenzo Ficarra
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ABSTRACT: PURPOSE: To perform a formal external validation of the preoperative Karakiewicz nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large series of surgically treated patients diagnosed with organ-confined or metastatic renal cell carcinoma (RCC). METHODS: Patient population originated from a series of retrospectively gathered cases that underwent radical or partial nephrectomy between years 1995 and 2007 for suspicion of kidney cancer. The original Cox coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10 years following surgery and compared to the observed risk of CSS in the current population. External validation was quantified using measures of predictive accuracy, defined as model discrimination and calibration. RESULTS: A total of 3,374 patients were identified. Relative to the original development cohort, the current sample population had a larger proportion of patients with localized (40.0 vs. 26.3 %, P < 0.001) and non-metastatic (92.2 vs. 88.1 %, P = 0.03) disease at presentation. Model discrimination for the prediction of CSS was 87.8 % (95 % CI, 84.4-91.4) at 1 year, 87.0 % (95 % CI, 84.4-89.5) at 2 years, 84.7 % (95 % CI, 82.3-87.1) at 5 years, and 85.9 % (95 % CI, 83.2-88.6) at 10 years. The relationship between predicted and observed CSS risk was adequate in the calibration plot. CONCLUSION: The use of the KN for the prediction of CSS in patients diagnosed with renal cell carcinoma was validated in the current study. In consequence, this tool may be recommended for routine clinical counseling in patients with various stages of RCC in the preoperative setting.
World Journal of Urology 07/2012; · 2.41 Impact Factor
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Sabine Brookman-May,
Matthias May,
Shahrokh F Shariat,
Evanguelos Xylinas,
Christian Stief,
Richard Zigeuner,
Thomas Chromecki,
Maximilian Burger,
Wolf F Wieland,
Luca Cindolo, [......],
Giacomo Novara, Marco Carini,
Andrea Minervini,
Claudio Simeone,
Alessandro Antonelli,
Vincenzo Mirone,
Nicola Longo,
Alchiede Simonato,
Giorgio Carmignani,
Vincenzo Ficarra
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ABSTRACT: BACKGROUND: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). OBJECTIVE: To determine features associated with late recurrence. DESIGN, SETTING, AND PARTICIPANTS: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). INTERVENTIONS: Patients underwent radical nephrectomy or nephron-sparing surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p<0.001), Fuhrman grade 3-4 (OR: 1.60; p=0.001), and pT stage >pT1 (OR: 2.28; p<0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p<0.001), pT stage (HR: 1.24; p<0.001), Fuhrman grade (HR: 2.40; p<0.001), age (HR: 1.01; p<0.001), and gender (HR: 0.71; p=0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. CONCLUSIONS: LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.
European urology 06/2012; · 7.67 Impact Factor
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European urology 06/2012; 62(3):e63-4. · 7.67 Impact Factor
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Expert Review of Anti-infective Therapy 06/2012; 12(6):699-701. · 2.65 Impact Factor
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Maria Lucia Angelotti,
Elisa Ronconi,
Lara Ballerini,
Anna Peired,
Benedetta Mazzinghi,
Costanza Sagrinati,
Eliana Parente,
Mauro Gacci, Marco Carini,
Mario Rotondi,
Agnes B Fogo,
Elena Lazzeri,
Laura Lasagni,
Paola Romagnani
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ABSTRACT: Recent studies implicated the existence in adult human kidney of a population of renal progenitors with the potential to regenerate glomerular as well as tubular epithelial cells and characterized by coexpression of surface markers CD133 and CD24. Here, we demonstrate that CD133+CD24+ renal progenitors can be distinguished in distinct subpopulations from normal human kidneys based on the surface expression of vascular cell adhesion molecule 1, also known as CD106. CD133+CD24+CD106+ cells were localized at the urinary pole of Bowman's capsule, while a distinct population of scattered CD133+CD24+CD106- cells was localized in the proximal tubule as well as in the distal convoluted tubule. CD133+CD24+CD106+ cells exhibited a high proliferative rate and could differentiate toward the podocyte as well as the tubular lineage. By contrast, CD133+CD24+CD106- cells showed a lower proliferative capacity and displayed a committed phenotype toward the tubular lineage. Both CD133+CD24+CD106+ and CD133+CD24+CD106- cells showed higher resistance to injurious agents in comparison to all other differentiated cells of the kidney. Once injected in SCID mice affected by acute tubular injury, both of these populations displayed the capacity to engraft within the kidney, generate novel tubular cells, and improve renal function. These properties were not shared by other tubular cells of the adult kidney. Finally, CD133+CD24+CD106- cells proliferated upon tubular injury, becoming the predominating part of the regenerating epithelium in patients with acute or chronic tubular damage. These data suggest that CD133+CD24+CD106- cells represent tubular-committed progenitors that display resistance to apoptotic stimuli and exert regenerative potential for injured tubular tissue.
Stem Cells 05/2012; 30(8):1714-25. · 7.78 Impact Factor
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European urology 05/2012; 62(2):e36-8. · 7.67 Impact Factor
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Linda Vignozzi,
Ilaria Cellai,
Raffaella Santi,
Letizia Lombardelli,
Annamaria Morelli,
Paolo Comeglio,
Sandra Filippi,
Federica Logiodice, Marco Carini,
Gabriella Nesi,
Mauro Gacci,
Marie-Pierre Piccinni,
Luciano Adorini,
Mario Maggi
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ABSTRACT: Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4(+)T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4(+)T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by T-cells, an increase in IL10, and a significant reduction of T cells proliferation suggested that DHT exerted a broad anti inflammatory effect on testosterone cells [corrected]. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.
Journal of Endocrinology 05/2012; 214(1):31-43. · 3.55 Impact Factor
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Urology 05/2012; 79(5):1124-5; author reply 1125. · 2.43 Impact Factor
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ABSTRACT: Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH).
To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up.
We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin.
International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance.
We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone.
The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.
Journal of Sexual Medicine 04/2012; 9(6):1624-33. · 3.55 Impact Factor
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Salvatore Siracusano,
Giacomo Novara,
Alessandro Antonelli,
Walter Artibani,
Roberto Bertini, Marco Carini,
Giorgio Carmignani,
Stefano Ciciliato,
Sergio Cosciani Cunico,
Nikolitsa Lampropoulou,
Nicola Longo,
Giuseppe Martorana,
Andrea Minervini,
Vincenzo Mirone,
Claudio Simeone,
Alchiede Simonato,
Claudio Valotto,
Filiberto Zattoni,
Vincenzo Ficarra
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ABSTRACT: Study Type - Therapy (multi-centre cohort) Level of Evidence 3b What's known on the subject? and What does the study add? In RCC about 5% of the patients presented multifocal disease. Prevalence of tumour multifocality was associated with a higher percentage of symptomatic RCC, higher pathological TNM stages, higher tumour grade and higher prevalence of tumour necrosis. Although in univariable analysis multifocal tumours had lower probability of CSS, tumour multifocality did not retain an independent predictive role in multivariable analysis. Patient age at surgery, gender, mode of presentation, pathological N stage and presence of metastases were independent predictors of CSS in multivariable analyses. OBJECTIVE: • To evaluate the prevalence and the prognostic role of multifocality in a large multi-institutional series of patients who underwent radical or partial nephrectomy for renal cell carcinoma (RCC). METHODS: • We retrospectively collected the data of 5378 patients who were surgically treated for RCC in 16 academic centres involved in the Surveillance and Treatment Update Renal Neoplasms (SATURN) project. • Univariable and multivariable Cox regression models addressed time to cancer-specific survival (CSS) after surgery. RESULTS: • Tumour multifocality was identified in 249 patients (5%). The median follow-up of the whole cohort was 42 months. At last follow-up, 786 (14.6%) were dead of cancer and 336 (6.2%) had experienced non-cancer-related death. • The 5- and 10-year CSS estimates were 84.1% and 77.3%, respectively, in patients with monofocal RCC, compared with 71.1% and 63.6%, respectively, in patients with multifocal disease (P < 0.001). • In univariable Cox regression analysis, tumour multifocality was significantly associated with CSS (hazard ratio [HR]= 1.83; P < 0.001). • On multivariate Cox regression analysis adjusted for the effects of other covariates, tumour multifocality did not retain an independent predictive value (HR = 1.24; P= 0.291). CONCLUSIONS: • In the present multi-institutional collaboration, about 5% of the patients presented multifocal RCC. • The presence of multifocal cancer was associated with some unfavourable clinical and pathological features. • Although in univariable analysis multifocal tumours had lower CSS probabilities, tumour multifocality did not retain an independent predictive role in multivariable analysis, once adjusted for the effect of the other clinical and pathological covariates.
BJU International 04/2012; · 2.84 Impact Factor
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Annamaria Morelli,
Paolo Comeglio,
Sandra Filippi,
Erica Sarchielli,
Ilaria Cellai,
Linda Vignozzi,
Ravit Yehiely-Cohen,
Elena Maneschi,
Mauro Gacci, Marco Carini,
Luciano Adorini,
Gabriella B Vannelli,
Mario Maggi
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ABSTRACT: In the male, metabolic syndrome (MetS) is associated to an increased risk of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). A recently established rabbit model of high fat diet (HFD)-induced MetS showed hypogonadism and the presence of prostate gland alterations, including inflammation, hypoxia and fibrosis. The present study investigated whether HFD-induced MetS might also alter bladder structure and function. Testosterone and the farnesoid X receptor (FXR) agonist INT-747, were evaluated for possible effects on HFD bladder. MetS rabbits develop bladder alterations, including fibrosis (reduced muscle/fiber ratio), hypoxia [2-fold increase as compared to regular diet (RD) group], low-grade inflammation (increased leukocyte infiltration and inflammatory markers) and RhoA/ROCK hyperactivity. Bladder strips from HFD rabbits, pre-contracted with carbachol, showed an overactive response to the selective ROCK inhibitor Y-27632. All these HFD-induced bladder alterations were partially blunted by testosterone and almost completely reverted by INT-747. Both treatments prevented some MetS features (glucose intolerance and visceral fat increase), thus suggesting that their effects on bladder could be ascribed to an improvement of the metabolic and/or hypogonadal state. However, a pathogenetic role for hypogonadism has been ruled out as GnRH analog-induced hypogonadal rabbits, fed a regular diet, did not show any detectable bladder alterations. In addition, INT-747 did not revert the MetS-induced hypogonadal state. FXR mRNA was highly expressed in rabbit bladder and positively associated with visceral fat increase. A direct effect of INT-747 on bladder smooth muscle was further suggested by inhibition of RhoA/ROCK-mediated activity by in vitro experiments on isolated cells. In conclusion, HFD-related MetS features are associated to bladder derangements, which are ameliorated by testosterone or INT-747 administration. INT-747 showed the most marked effects in counteracting MetS-related RhoA/ROCK overactivity, thus opening novel therapeutic opportunities for this drug.
The Journal of steroid biochemistry and molecular biology 03/2012; 132(1-2):80-92. · 2.66 Impact Factor
