Molecular markers for prostatic cancer.

Prostate cancer (caP) is a major public health problem. Many groups have attempted to identify prognostic risk factors to early detect caP and to identify who will need active treatment. Since the introduction of prostate specific antigen (PSA), diagnosis of caP has increased even as mortality for prostatic cancer has declined. Using current recommended guidelines, the PSA test suffers from both of limited specificity and sensitivity. With the aim to improve early detection of prostatic cancer the volume adjusted PSA, PSA isoforms and PSA kinetics have been investigated. Recently, technological advances in molecular assays have led to the discovery of new markers with high specificity. Further, proteomic array profiling and DNA methylation assays could provide for more accurate diagnosis and prognosis. Current evidence suggests that no single marker is likely to achieve the desired level of diagnostic and prognostic accuracy: future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer and to predict outcomes after therapies

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III

Objective: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. Material and methods: From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). Results: A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). Conclusions: In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies with greater sample size

Endothelial progenitor cells and erectile dysfunction: a brief review on diagnostic significance and summary of our experience.

The article provides a brief review of the literature concerning the diagnostic use of endothelial progenitor cells in patients with erectile dysfunction. In particular, patients with arterial erectile dysfunction could benefit from the use of this diagnostic marker, which in clinical practice can be used together with more conventional methods such as the penile Doppler. It is very important to acquire diagnostic tools for the diagnosis of sub clinical form of endothelial dysfunction in these patients, in particular when the erectile dysfunction is associated with cardiovascular risk factors

Different levels of Cd45pos leukocytes in the semen of patients with low testicular volume.

The aim of this study was to evaluate the concentrations of CD45pos leukocytes in the semen samples of infertile patients with low testicular volume (TV) compared to subjects with normal TV. The testis was considered normal in size when it had a volume between 15 and 25 cm3, low–normal with a volume between 10 and 12 cm3 and hypotrophic when the volume was <10 cm3. The patients with low testicular volume (<10 cm3) showed significantly higher concentrations of CD45pos leukocytes compared to other groups ( P <0.05). The correlation analysis showed the presence of a positive linear relationship between CD45pos leukocytes and the percentage of immature germ elements (r = 0.88; P <0.05) and between CD45pos leukocytes and the percentage of spermatozoa with phosphatidylserine externalisation (r = 0.90; P <0.05) as well as a negative linear relationship between the percentage of spermatozoa with normal morphology and the seminal CD45pos leukocyte concentrations ( r = −0.75; P <0.05). The results of this study showed that patients with low testicular volume (<10 cm3) have significantly increased CD45pos leukocyte concentrations associated with increased percentages of immature germ elements, spermatozoa with signs of early apoptosis and spermatozoa with abnormal morphology

Tailored treatment including radical prostatectomy and radiation therapy + androgen deprivation therapy versus exclusive radical prostatectomy in high-risk prostate cancer patients: results from a prospective study

Purpose To evaluate outcomes of patients with high risk prostate cancer (PCa) who underwent radical prostatectomy (RP) in a context of a multidisciplinary approach including adjuvant radiation (RT) + androgen deprivation therapy (ADT). Matherials and Methods 244 consecutive patients with high risk localized PCa underwent RP and bilateral extended pelvic lymph node dissection at our institution. Adjuvant RT + 24 months ADT was carried out in subjects with pathological stage ≥ T3N0 and/or positive surgical margins or in patients with local relapse. Results After a median follow-up was 54.17 months (range 5.4-117.16), 13 (5.3%) subjects had biochemical progression, 21 (8.6%) had clinical progression, 7 (2.9%) died due to prostate cancer and 15 (6.1%) died due to other causes. 136 (55.7%) patients did not receive any adjuvant treatment while 108 (44.3%) received respectively adjuvant or salvage RT+ADT. Multivariate Cox proportional hazard analysis showed that pre-operative PSA value at diagnosis is a significant predictive factor for BCR (HR: 1.04, p < 0.05) and that Gleason Score 8-10 (HR: 2.4; p<0.05) and PSMs (HR: 2.01; p < 0.01) were significant predictors for clinical progression. Radical prostatectomy group was associated with BPFS, CPFS, CSS and OS at 5-years of 97%, 90%, 95% and 86% respectively, while adjuvant radiation + androgen deprivation therapy group was associated with a BPFS, CPFS and CSS at 5-years of 91%, 83%, 95% and 88%, without any statistical difference. Conclusions Multimodality tailored treatment based on RP and adjuvant therapy with RT+ADT achieve similar results in terms of OS after 5-years of follow-up

Detection rate for significant cancer at confirmatory biopsy in men enrolled in Active Surveillance protocol: 20 cores vs 30 cores vs MRI/TRUS fusion prostate biopsy

Introduction: The detection rate for significant prostate cancer of extended vs saturation vs mMRI/TRUS fusion biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol. Mterials and methods: From May 2013 to September 2016 75 men aged 66 years (median) with very low risk PCa were enrolled in an AS protocol and elegible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density &lt; 0.20, 2 &lt; unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core &lt; 50%. All patients underwent 3.0 Tesla pelvic mpMRI before confirmatory transperineal extended (20 cores) or saturation biopsy (SPBx; 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (4 cores) of suspicious lesions (PI-RADS 3-5). Results: 21/75 (28%) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI lesions PI-RADS 4-5 vs PI-RADS 3-5 diagnosed 9/21 (42.8%) vs 16/21 (76.2%) significant PCa with 2 false positives (6.5%). The detection rate for significant PCa was equal to 76.2% (mpMRI/TRUS fusion biopsy) vs 81% (extended) vs 100% (SPBx) (p = 0.001); mpMRI/TRUS targeted biopsy and extended biopsy missed 5/21 (23.8%) and 4/21 (19%) significant PCa which were found by SPBx (p = 0.001) being characterised by the presence of a single positive core of GS ≥ 7 with GPC &lt; 10%. Conclusions: Although mpMRI improve the diagnosis of clinically significant PCa, SPBx is provided of the best detection rate for PCa in men enrolled in AS protocols who underwent confirmatory biopsy

Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy

Objective: To compare the prognostic accuracy of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of patients who underwent radical prostatectomy (RP) for prostate cancer (PCa). Methods and materials: We evaluated 156 patients with biopsy-proven, clinically localized PCa who underwent RP between January 2013 and December 2013 at 2 tertiary care institutions. Blood and urinary specimens were collected before initial prostate biopsy for [-2] pro-prostate-specific antigen (PSA), its derivates, and PCA3 measurements. Univariate and multivariate logistic regression analyses were carried out to determine the variables that were potentially predictive of tumor volume >0.5. ml, pathologic Gleason sum 657, pathologically confirmed significant PCa, extracapsular extension, and seminal vesicles invasions. Results: On multivariate analyses and after bootstrapping with 1,000 resampled data, the inclusion of PHI significantly increased the accuracy of a baseline multivariate model, which included patient age, total PSA, free PSA, rate of positive cores, clinical stage, prostate volume, body mass index, and biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to predict tumor volume>0.5, the addition of PHI to the baseline model significantly increased predictive accuracy by 7.9% (area under the receiver operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did not lead to a significant increase.Although both PHI and PCA3 significantly improved predictive accuracy to predict extracapsular extension compared with the baseline model, achieving independent predictor status (all P's<0.01), only PHI led to a significant improvement in the prediction of seminal vesicles invasions (AUC = 92.2, P<0.05 with a gain of 3.6%).In the subset of patients with GS 646, PHI significantly improved predictive accuracy by 7.6% compared with the baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs. 89.0) to predict pathologic GS 657. For these outcomes, PCA3 did not add incremental predictive value. Conclusions: In a cohort of patients who underwent RP, PHI is significantly better than PCA3 in the ability to predict the presence of both more aggressive and extended PCa

Conversion to Sirolimus Therapy in Kidney Transplant Recipients with New Onset Diabetes Mellitus after Transplantation

New-onset diabetes mellitus after transplantation (NODAT) may complicate 2–50% of kidney transplantation, and it is associated with reduced graft and patient survivals. In this retrospective study, we applied a conversion protocol to sirolimus in a cohort of kidney transplant recipients with NODAT. Among 344 kidney transplant recipients, 29 patients developed a NODAT (6.6%) and continued with a reduced dose of calcineurin inhibitors (CNI) (8 patients, Group A) or were converted to sirolimus (SIR) (21 patients, Group B). NODAT resolved in 37.5% and in 80% patients in Group A and Group B, respectively. In Group A, patient and graft survivals were 100% and 75%, respectively, not significantly different from Group B (83.4% and 68%, resp., P=0.847). Graft function improved after conversion to sirolimus therapy: serum creatinine was 1.8 ± 0.7 mg/dL at the time of conversion and 1.6 ± 0.4 mg/dL five years after conversion to sirolimus therapy (P<0.05), while in the group of patients remaining with a reduced dose of CNI, serum creatinine was 1.7 ± 0.6 mg/dL at the time of conversion and 1.65 ± 0.6 mg/dL at five-year followup (P=0.732). This study demonstrated that the conversion from CNI to SIR in patients could improve significantly the metabolic parameters of patients with NODAT, without increasing the risk of acute graft rejection