Francesco Mistretta

Long-term oncologic outcomes of laparoscopic renal cryoablation as primary treatment for small renal masses

INTRODUCTION Data regarding long-term oncologic outcomes of laparoscopic renal cryoablation (LRC) as first treatment for small renal masses (SRMs) are lacking. We hypothesized that LRC might provide an effective long-term cancer control in patients with a single cT1a SRM without a previous history of renal cell carcinoma (RCC). MATERIALS AND METHODS The study design was a retrospective analysis of 174 consecutive patients who received LRC as first treatment for a single computed tomography or magnetic resonance imaging contrast-enhancing cT1a SRM between 2000 and 2013. Patients with a previous history of RCC were excluded. Treatment failure was evaluated 1 day after surgery. Local recurrence, metachronous SRM, systemic progression, disease relapse, cancer-specific mortality, and all-cause mortality were evaluated 10 years after surgery. Kaplan-Meier plots were used to depict outcome-free survival rate. RESULTS Median patient age was 66 years. Median tumor size was 20mm. Median follow-up was 48 months. Among patients with biopsy-proven RCC (63%, n = 109), the treatment failure-free rate was 98%. The 10-year recurrence-free survival rate was 95% and the 10-year metachronous SRM-free survival rate was 87%. The 10-year systemic progression-free survival rate was 100% and the 10-year disease relapse-free survival rate was 81%. The cancer-specific mortality-free survival rate was 100%, and the all-cause mortality-free survival rate was 61%. CONCLUSIONS LRC provides safe long-term cancer control in patients newly diagnosed with a single cT1a SRM. Treatment failure and local recurrence are uncommon. Systemic progression-free survival and cancer-specific-free survival are optimal.

Clinical performance of serum isoform [‐2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study

To test the hypothesis that [‐2]proPSA (p2PSA) and its derivatives are more accurate than total prostate‐specific antigen (tPSA), free prostate‐specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years.

The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats

To study micturition and bladder overactivity in female rats after chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide (OEtA).

Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta‐analysis

To evaluate the influence of posterior musculofascial plate reconstruction (PR) on early return of continence after radical prostatectomy (RP); an updated systematic review of the literature. A systematic review of the literature was performed in June 2015, following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement and searching Medline, Embase, Scopus and Web of Science databases. We searched the terms posterior reconstruction prostatectomy, double layer anastomosis prostatectomy across the ‘Title’ and ‘Abstract’ fields of the records, with the following limits: humans, gender (male), and language (English). The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. A meta‐analysis of the risk ratios estimated using data from the selected studies was performed. In all, 21 studies were identified, including three randomised controlled trials. The overall analysis of comparative studies showed that PR improved early continence recovery at 3–7, 30, and 90 days after catheter removal, while the continence rate at 180 days was statistically but not clinically affected. Statistically significantly lower anastomotic leakage rates were described after PR. There were no significant differences for positive surgical margins rates or for complications such as acute urinary retention and bladder neck stricture. The analysis confirms the benefits at 30 days after catheter removal already discussed in the review published in 2012, but also shows a significant advantage in terms of urinary continence recovery in the first 90 days. A multicentre prospective randomised controlled trial is currently being conducted in several institutions around the world to better assess the effectiveness of PR in facilitating an earlier recovery of postoperative urinary continence.

Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: Data from the PROMEtheuS project, a multicentre European prospective study

To test serum prostate‐specific antigen (PSA) isoform [‐2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients.

Clinical Use of [-2]proPSA (p2PSA) and Its Derivatives (%p2PSA and Prostate Health Index) for the Detection of Prostate Cancer: A Review of the Literature

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physicians ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.

Urethral Lift for Benign Prostatic Hyperplasia: A Comprehensive Review of the Literature

Current treatments for benign prostatic hyperplasia (BPH) include watchful waiting, medical therapy, and interventional procedures. The post-surgical complication profile and the early discontinuation of medical therapy are significant drawbacks of the established approach and stimulate the search for less-invasive approaches. Our aim is to provide a comprehensive review all available literature on prostatic urethral lift (PUL), presenting an overview of safety, indications, surgical technique and results of the procedure, and to evaluate the potential role it could play in the treatment of BPH. A comprehensive search was conduct on PubMed and Scopus database to identify original articles in English dealing with PUL without any limit to publication date. Keywords used were prostatic urethral lift, urethral lifting, Urolift, benign prostatic hyperplasia and minimally invasive therapy. The PUL seems to offer a better IPSS improvement when compared to medical therapy, but the result is inferior when compared to surgical therapy. Published studies report an absence of degradation of erectile or ejaculatory function after treatment, which appears a noteworthy benefit of PUL. Additional advantages of the PUL are a better complication profile in comparison to other surgical therapies and the use of a local anesthesia, sometimes without postoperative catheterization. The PUL, a novel, minimally invasive treatment option for men affected by BPH, presents a promising potential although it is clear that PUL is not a substitute for traditional ablative surgical approach, as this procedure requires a scrupulous selection of the patient.

Preoperative prostate health index is an independent predictor of early biochemical recurrence after radical prostatectomy: Results from a prospective single-center study.

BACKGROUND The aim of this study was to test the hypothesis that preoperative prostate health index (PHI) levels could help to predict early biochemical recurrence (BCR) in a contemporary population of patients with prostate cancer treated with robot-assisted radical prostatectomy (RARP). METHODS The study population consisted of 313 patients treated with RARP for clinically localized prostate cancer at a single institution between 2010 and 2011. Patients subjected to neoadjuvant or adjuvant therapies and patients with a follow-up of<2 years were excluded. BCR was defined as a postoperative level of total prostate-specific antigen ≥0.2 ng/ml and elevating after RARP. The minimum P-value method was used to determine the most significant PHI cutoff value to discriminate between patients with and without BCR. The Kaplan-Meier method was used to determine BCR-free survival rates. Finally, Cox regression models were fitted to determine the predictors of BCR, and the predictive accuracy (area under the curve) of each predictor was determined with the Harrell concordance index. RESULTS Mean total prostate-specific antigen and mean PHI levels were 5.76 ng/ml (interquartile range: 4.2-8.7) and 46.0 (35-62), respectively. Biopsy Gleason score was 6 in 173 (55.3%), 7 in 121 (38.7%), and ≥8 in 19 (6.1%) patients. At final pathology, extracapsular extension was observed in 59 (18.8%), seminal vesicle invasion in 24 (7.7%), and lymph node invasion in 11 (3.5%) patients, whereas 228 (72.8%) patients had organ-confined disease. The 2-year BCR-free survival rate was 92.5% in the overall population and was 96.7% in patients with organ-confined disease. The most significant PHI cutoff value to discriminate between patients with and without BCR was 82. Specifically, the 2-year BCR-free survival rate was 97.7% in patients with a preoperative PHI level<82 relative to 69.7% in patients with a PHI level ≥82 (log-rank test: P<0.001). Finally, in multivariable Cox regression analyses, PHI level emerged as an independent predictor of BCR in both the preoperative and the postoperative settings and was more accurate than several established BCR predictors were. CONCLUSIONS Preoperative PHI levels may discriminate between patients who are at a high risk vs. low risk of BCR after RARP. External validation of our findings within a larger population with a longer follow-up time is needed.

Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy.

AbstractTo evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa.This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10 ng/mL; clinical stage <T3a; biopsy Gleason score <7; prostate mpMRI performed preoperatively at our Institution; intraoperative FSA of the posterolateral aspects of the specimen.All the identified lesions were scored according to the Prostate Imaging Reporting and Data System (PIRADS). We considered the lesion with the highest PIRADS score as index lesion. All the included patients underwent nerve-sparing RARP. During surgery, the specimen was sent for FSA of the posterolateral aspects. The surgeon, according to the localization scheme provided by the mpMRI, inked the region of the posterolateral aspect of the prostate that had to be submitted to FSA.We evaluated association between clinical features and PSM, upgrading, upstaging, and presence of unfavorable disease.Two hundred fifty-four patients who underwent nerve-sparing RARP were included. PSM rate was 29.13% and 15.75% at FSA and final pathology respectively. Interestingly, the use of FSA reduced PSM rate in pT3 disease (25.81%). Higher PIRADS scores demonstrated to be related to high probability of upgrading and upstaging. This significativity remains even when considering PIRADS 2–3 versus 4 versus 5 and PIRADS 2–3 versus 4–5. Also PSM at FSA were associated with higher probability of upgrading and upstaging.PIRADS score and FSA resulted to be strictly related to grading and staging, thus being able to predict upgrading and/or upstaging at final pathology.

Bladder Cancer and Urothelial Impairment: The Role of TRPV1 as Potential Drug Target

Urothelium, in addition to its primary function of barrier, is now understood to act as a complex system of cell communication that exhibits specialized sensory properties in the regulation of physiological or pathological stimuli. Furthermore, it has been hypothesized that bladder inflammation and neoplastic cell growth, the two most representative pathological conditions of the lower urinary tract, may arise from a primary defective urothelial lining. Transient receptor potential vanilloid channel 1 (TRPV1), a receptor widely distributed in lower urinary tract structures and involved in the physiological micturition reflex, was described to have a pathophysiological role in inflammatory conditions and in the genesis and development of urothelial cancer. In our opinion new compounds, such as curcumin, the major component of turmeric Curcuma longa, reported to potentiate the effects of the chemotherapeutic agents used in the management of recurrent urothelial cancer in vitro and also identified as one of several compounds to own the vanillyl structure required to work like a TRPV1 agonist, could be thought as complementary in the clinical management of both the recurrences and the inflammatory effects caused by the endoscopic resection or intravesical chemotherapy administration or could be combined with adjuvant agents to potentiate their antitumoral effect.