Targeting of H19/cell adhesion molecules circuitry by GSK-J4 epidrug inhibits metastatic progression in prostate cancer.

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.

H19-Dependent Transcriptional Regulation of ß3 and ß4 Integrins Upon Estrogen and Hypoxia Favors Metastatic Potential in Prostate Cancer.

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.

Intraprostatic botulinum toxin type "A" injection in patients with benign prostatic hyperplasia and unsatisfactory response to medical therapy: A randomized, double-blind, controlled trial using urodynamic evaluation.

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.

Colorectal cancer in the young: a possible role for immune surveillance?

BACKGROUND: Younger patients with colorectal cancer (CRC) generally have better survival in spite of worse clinical and pathological features. METHODS: Twenty-six patients under 50 years operated for primary CRC were enrolled and matched 1:2:2 according to stage, tumor site and gender with 52 patients from 50 to 70 years and 52 patients over 70 years old. RESULTS: Patients under 50 years had a significantly longer overall, cancer specific and disease free survival (p = .001, p = .007 and p = .05, respectively). However, they had more frequently lymphovascular invasion (p = .006) and they more frequently developed metachronous CRC at follow-up (p = .03). Nevertheless, preoperative lymphocytes blood count/white blood count (LBC/WBC) ratio inversely correlated with age at operation (rho = -.21, p = .04) and it predicted CRC recurrence with an accuracy of 70%, p < .001 (threshold value LBC/WBC = 0.21%) and better overall, cancer specific and disease free survival (p < .0001 for all). At multivariate analysis, stage and LBC/WBC ratio resulted independent predictors of disease free survival (p = .0001 and p = .01, respectively). CONCLUSIONS: Patients under 50 years had a significantly longer survival with a higher LBC/WBC ratio. These results could suggest a possible role of immunosurveillance in neoplastic control.

A circulating miRNA assay as a first-line test for prostate cancer screening.

BACKGROUND: Prostate cancer (PCa) screening currently relies on prostate-specific antigen (PSA) testing and digital rectal examination. However, recent large-scale studies have questioned the long-term efficacy of these tests, and biomarkers that accurately identify PCa are needed. METHODS: We analysed the levels of circulating microRNAs (miRNAs) in patients with elevated PSA who were diagnosed with either localised PCa (n=36) or benign prostatic hyperplasia (BPH, n=31) upon biopsy. Real-time RT-PCR with Taqman probes was used to measure plasma levels of miRNAs. To circumvent problems associated with circulating miRNA quantitation, we computed the expression ratios of upregulated and downregulated miRNAs. RESULTS: The miR-106a/miR-130b and miR-106a/miR-223 ratios were significantly different between the biopsy-positive and BPH groups (P<0.0001), and yielded statistical power values that were >0.99. Both miRNA ratios were highly sensitive and more specific than PSA in discriminating localised PCa from BPH. Receiver operating characteristic curve analysis revealed area under curve values of 0.81 (miR-106a/miR-130b) and 0.77 (miR-106a/miR-223). CONCLUSIONS: Testing for circulating miR-106a/miR-130b and miR-106a/miR-223 ratios may reduce the costs and morbidity of unnecessary biopsies and is feasible for large-scale screening, as it requires measuring only three miRNAs.

Pheromonal Cues Deposited by Mated Females Convey Social Information about Egg-Laying Sites in Drosophila Melanogaster.

Individuals can make choices based on information learned from others, a phenomenon called social learning. How observers differentiate between which individual they should or should not learn from is, however, poorly understood. Here, we showed that Drosophila melanogaster females can influence the choice of egg-laying site of other females through pheromonal marking. Mated females mark territories of high quality food by ejecting surplus male sperm containing the aggregation pheromone cis-11-vaccenyl acetate (cVA) and, in addition, deposit several sex- and species-specific cuticular hydrocarbon (CHC) pheromones. These pheromonal cues affect the choices of other females, which respond by preferentially laying eggs on the marked food. This system benefits both senders and responders, as communal egg laying increases offspring survival. Virgin females, however, do not elicit a change in the egg-laying decision of mated females, even when food has been supplemented with ejected sperm from mated females, thus indicating the necessity for additional cues. Genetic ablation of either a female's CHC pheromones or those of their mate results in loss of ability of mated females to attract other females. We conclude that mated females use a pheromonal marking system, comprising cVA acquired from male ejaculate with sex- and species-specific CHCs produced by both mates, to indicate egg-laying sites. This system ensures information reliability because mated, but not virgin, females have both the ability to generate the pheromone blend that attracts other flies to those sites and a direct interest in egg-laying site quality.

OnabotulinumtoxinA injection therapy in men with LUTS due to primary bladder-neck dysfunction: objective and patient-reported outcomes.

OBJECTIVE: To determine efficacy and safety of OnabotulinumtoxinA (BoNT-A) injection therapy in medically refractory patients with lower urinary tract symptoms (LUTS) due to primary bladder-neck dysfunction (PBND). MATERIALS AND METHODS: Thirty-five consecutive ambulatory males diagnosed with PBND and refractory to medical therapy, with IPSS > 15, Qmax < 15 ml/sec, and total prostate volume < 30 cm(3), were screened from January 2010 to December 2011. Eligible patients underwent transurethral bladder-neck injection of BoNT-A (200 U, 50 U/ml × 4 sites) and were assessed at baseline, 2-, 6-, 9-, and 12-month postprocedure and until duration of clinical response. The primary outcome was the change from baseline in total IPSS, and secondary outcome were storage- and voiding-IPSS, QoL score, Qmax, and postvoiding residual volume (PVR), patient-reported outcomes. Adverse effects were also recorded, including ejaculatory dysfunctions. RESULTS: Of 30 enrolled patients (mean age 33.8 years), 29 (96.7%) completed the study. A statistically significant improvement of total IPSS was observed from 21.9 at baseline, to 7.8, 10.3, and 16.6 at 2, 6, and 9 months, respectively (P < 0.000). Statistically significant improvements from baseline of storage- and voiding-IPSS, QoL score, Qmax, and PVR were also observed until 9-month postprocedure. The proportion of patients with overall satisfaction was favorable although decreasing from 80% at 2 months, to 44.8% at 12 months. No significant adverse effects or ejaculatory dysfunctions were noted. CONCLUSIONS: BoNT-A injection therapy appears effective and safe in medically refractory men with PBND, although repeated procedures are required for long-term sustained benefit. Randomized controlled trials are warranted in order to corroborate these results.

Brachytherapy: The urologist opinion.

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.

Comparison of PIV and Other Immune Inflammation Markers of Oncological and Survival Outcomes in Patients Undergoing Radical Cystectomy.

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.

Predictive Factors for Major Complications and Urological Cancer Diagnosis in Older Adults (≥80 Years) Admitted to the Emergency Department for Hematuria.

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.

Sexual outcomes after organ potency-sparing surgery and glans reconstruction in patients with penile carcinoma.

INTRODUCTION: Radical surgery is the "gold standard" for treatment of invasive penile carcinoma but very poor aesthetic, functional and psychological outcomes have been reported. Our purpose was to assess the impact of organ potency-sparing surgery in locally confined carcinoma of the penis. MATERIALS AND METHODS: We evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2), treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of cavernosal apexes, or glandulectomy and limited apical resection in cases of Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15 questionnaire before the appearance of neoplasia (about three months before the surgery) and six months after surgery. Quality of life was evaluated by the Bigelow-Young questionnaire. The scores relating to two weeks prior to the surgery have been compared to those obtained six months after surgery. The statistical analysis was conducted using t-Student for repeated measures and analysis of variance. RESULTS: Six months after surgery 73% of patients reported spontaneous rigid erections, 60% coital activity while 76% of the group treated with urethral glanduloplasty reported normal ejaculation and orgasm, regained an average of 35 days after surgery. The average IIEF-15 scores reported in the entire series in the domains of erection, libido and coital activity of the pre-cancer period were not statistically different than those recorded six months after surgery. In the group treated with glandular reconstruction, pre-and postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were not significantly different. Mean scores of Bigelow-Young questionnaires related to sexual pleasure, familial, social and professional relationships showed significant improvement after surgery. CONCLUSIONS: Potency sparing-sparing surgical treatments have a positive impact on a wide spectrum of the patient's life including family relationships, and social and working conditions.

Value of transrectal color Doppler ultrasound of the common penile arteries in the diagnosis of arteriogenic erectile dysfunction: A pilot study.

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.

Determinants of renal papillary appearance in kidney stone formers: An in-depth examination.

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 defined 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 confirmed 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 significant correla-tions were found. CONCLUSIONS: Our results confirm the lack of efficacy 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.

Efficacy of an assisted low-intensity programme of perioperative pelvic floor muscle training in improving the recovery of continence after radical prostatectomy: a randomized controlled trial.

UNLABELLED: Study Type - Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Peri-operative pelvic floor muscle training reduces urinary incontinence for men undergoing radical prostatectomy (RP). A preoperative biofeedback session, combined with postoperative pelvic floor muscle training, and assisted sessions on a monthly basis only, is an effective low-intensity programme to improve recovery of continence in patients undergoing RP. OBJECTIVE: To evaluate the efficacy of preoperative biofeedback (BFB) combined with an assisted low-intensity programme of postoperative perineal physiokinesitherapy in reducing the incidence, duration and severity of urinary incontinence (UI) in patients undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A prospective, single-centre, randomized controlled clinical study was designed. • The intervention group received a training session with BFB, supervised oral and written instructions on Kegel exercises and a structured programme of postoperative exercises on the day before open RP. After RP, patients received control visits, including a session of BFB, at monthly intervals only. • The control group received, after catheter removal, only oral and written instructions on Kegel exercises to be performed at home. Patients received control visits at 1, 3 and 6 months after catheter removal. • At each visit the number of incontinence episodes, the number of pads used and patient-reported outcome measures (International Consultation on Incontinence Questionnaire on Urinary Incontinence [ICIQ-UI], [ICIQ]-Overactive Bladder [OAB], University of California, Los Angeles-Prostate Cancer Index [UCLA-PCI], International Prostate Symptom Score-Quality of Life [IPSS-QoL]) were assessed in both groups. All patients were followed-up for a period of at least 6 months after catheter removal. • The primary outcome was the recovery of continence, strictly defined as a ICIQ-UI score of zero. RESULTS: Overall, 34 consecutive patients were eligible and 32 were available for the final analysis: 16 patients for each study group. The two groups were homogeneous for all pre- and intraoperative features examined. • In the intervention group, continence had been achieved by six, eight and 10 patients at 1-, 3- and 6-month follow-ups, respectively, vs no patients (P= 0.02), one patient (P= 0.01) and one patient (P= 0.002) in the control group at each follow-up, respectively. • The analysis of the UCLA-PCI and ICIQ-OAB scores, the number of incontinence episodes per week and the number of pads per week showed significant differences in favour of patients in the intervention group at 3 and 6 months. • Patients in the intervention group reported better IPSS-QoL scores at all follow-up times but the difference did not reach statistical significance. CONCLUSIONS: Preoperative BFB combined with a postoperative programme of perineal physiokinesitherapy and assisted sessions on a monthly basis only, is a treatment strategy significantly more effective than the standard care in improving recovery of continence in patients undergoing RP. • The impact on QoL appeared less evident, although a trend for a better QoL was observed in the intervention group.

Patient-reported outcomes in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with intraprostatic OnabotulinumtoxinA: 3-month results of a prospective single-armed cohort study.

UNLABELLED: Study Type--Therapy (prospective cohort) Level of Evidence 3a. What's known on the subject? and What does the study add? Several short-term studies have shown that intraprostatic injection of botulinum toxin (BTX) improves lower urinary tract symptoms and flow parameters in patients with BPH, but information on patient-reported outcomes is lacking. The present study provides useful data on patient-perceived level of improvement and effectiveness of intraprostatic injection of BTX, as well as on patient's satisfaction with this therapy. Short-term results are promising and comparable with those reported with standard pharmacological therapy. OBJECTIVE: • To evaluate patient-reported and objective outcomes after intraprostatic injection of OnabotulinumtoxinA (BTX-A) in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: • A prospective single-armed cohort study was designed. • Patients diagnosed with LUTS due to BPH and unsatisfactory response to medical therapy, were recruited between November 2010 and July 2011. • Patients received transperineal injection of 200 U BTX-A in the transition zone, under transrectal ultrasonographic guidance. • The outcome assessment was performed at 3 months and included a patient-reported outcomes (PROs) questionnaire with questions on patient global impression of improvement (PGI-I, 0-6 point scale), of satisfaction (PGI-S, 0-5 point scale), and of efficacy (PGI-E, 0-5 point scale). RESULTS: • Of 75 screened patients, 64 with a mean (sd) age of 63 (9.3) years were available for the outcome assessment. • Patients reported a mean reduction of 49% in International Prostate Symptom Score (IPSS), which decreased from 19.7 (7.7) to 10 (7.1) (P < 0.001), and a mean reduction of 44% in IPSS-health-related quality of life item score, from 4.17 (1.2) to 2.3 (1.6) (P < 0.001). • There was a 33% increase in maximum urinary flow rate (P < 0.001) and an 80% reduction in postvoid residual urine volume (P < 0.001). • In all, 36 (56%) patients had a subjective improvement in LUTS (PGI-I ≥ 4), 43 (67%) reported satisfaction with the treatment (PGI-S ≥ 3), and 44 (68%) judged the treatment as effective (PGI-E ≥ 3). In all, 50 (79%) patients would repeat the same treatment under the same circumstances, while 54 (84%) would recommend the treatment to another person with the same diagnosis. • There was a statistically significant positive correlation between patients' satisfaction and both baseline IPSS (ρ 0.441, P < 0.001) and reduction rate of the IPSS (ρ 0.850, P < 0.001). CONCLUSIONS: • Intraprostatic injection of BTX-A in men with LUTS due to BPH provides clinically significant short-term subjective and objective benefit. • Increasing severity of baseline LUTS appears moderately associated with the patient-perceived benefit from the treatment. • Although the non-randomised design and short-term assessment limit the level of evidence of our study, intraprostatic BTX-A seems a promising, safe and minimally invasive option for patients with BPH with unsatisfactory response to standard drug therapy.

Imaging in prostate cancer staging: present role and future perspectives.

Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related mortality. Thus, although survival rate continues to improve, prostate cancer remains a compelling medical health problem. The major goal of prostate cancer imaging in the next decade will be more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information in order to plan the most appropriate therapeutic strategy. No consensus exists regarding the use of imaging for evaluating primary prostate cancer. However, conventional and functional imaging are expanding their role in detection and local staging and, moreover, functional imaging is becoming of great importance in oncologic management and monitoring of therapy response. This review presents a multidisciplinary perspective on the role of conventional and functional imaging methods in prostate cancer staging.

Complications of extracorporeal shock wave lithotripsy for urinary stones: to know and to manage them-a review.

To identify the possible complications after extracorporeal shock wave lithotripsy (SWL) and to suggest how to manage them, the significant literature concerning SWL treatment and complications was analyzed and reviewed. Complications after SWL are mainly connected to the formation and passage of fragments, infections, the effects on renal and nonrenal tissues, and the effects on kidney function. Each of these complications can be prevented adopting appropriate measures, such as the respect of the contraindications and the recognition and the correction of concomitant diseases or infection, and using the SWL in the most efficient and safe way, tailoring the treatment to the single case. In conclusion, SWL is an efficient and relatively noninvasive treatment for urinary stones. However, as with any other type of therapy, some contraindications and potential complications do exist. The strictness in following the first could really limit the onset and danger of the appearance of others, which however must be fully known so that every possible preventive measure be implemented.

Hot topics in urological health economics. A mini review.

Urological diseases are becoming a major public health problem. In fact, they increasingly weigh on the economy of a country due to the high direct costs and the consequent significant loss of productivity. Prostate cancer represents 11% of the costs for the treatment of all cancers in the United States with $8 billion and a cost per-patient from diagnosis to death of $81,658. Instead bladder cancer has the higher costs per-patient in terms of medical care, from diagnosis until death (U.S. $ 96,553). In Italy, in a reference hospital, the average costs of non muscle-invasive forms treated with endoscopic resection (TURB) and infiltrating forms treated with radical cystectomy are approximately Euro 2242.20 and Euro 6860 respectively, but they increase due to the follow-up and the ancillary treatments. In the field of functional disease, in the U.S. the average annual expenditure per capita for incontinence, including inpatient and outpatient services is $1382. While for patients who had undergone surgery the average total spending rose to $3620. For overactive bladder the total cost in the United States is estimated at 12.02 billion U.S. dollars, with $9.17 billion allocated to the community costs and $ 2.85 billion for institutional costs. However, further pharmacoeconomic studies are required to better understand the net economic impact of any alternative strategies to those actually present. Stone disease is a highly prevalent and costly condition for which United States total health care expenditures, in the year 2000, were estimated to be almost $ 2.1 billion. Treatment of nephrolithiasis depends on stone size and location, but typically involves a surgical procedure such as extracorporeal shock wave lithotripsy (ESWL), ureteroscopic laser lithotripsy, percutaneous nephrostolithotomy (PCNL) or open stone surgery with an average expenditure per procedure of $2295, $1425, $3624, $2916 respectively.

Mechanisms of Resistance to Second-Generation Antiandrogen Therapy for Prostate Cancer: Actual Knowledge and Perspectives.

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.

Laser technology in urologic oncology.

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.