Vincenzo Gentile

Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: A retrospective analysis

OBJECTIVES We analyze our experience on BPH through 20 years of histopathological examinations performed by the same pathologist. METHODS We retrospectively reviewed all histopathological examinations performed from January 1979 to December 1998 in patients undergoing surgery in our urological clinic who were diagnosed with BPH. We limited our evaluation to the following variables in each BPH case analyzed: inflammatory aspects associated with BPH, presence of focal acinar atrophy, atypical adenomatous hyperplasia (AAH), prostatic intraepithelial neoplasia (PIN), incidental prostate carcinoma (IC). These histological variables were analyzed according to some clinical parameters such as age, prostate volume and serum PSA. RESULTS The study population was comprised of 3942 cases with histological diagnosis of BPH. The mean patient age was 68.85+/-7.67 years. In particular, inflammatory aspects were associated with BPH in a high percentage of cases (43.1% =1700 cases), predominantly as chronic inflammation. Observation of focal acinar atrophy significantly increased according to patient decade of age (p=0.027). There was a significant trend to increase with age decades (p=0.036) for high grade PIN. A significant difference was found in IC (T1a, T1b) distribution in the different decades of age and especially in regards to both T1a and T1b tumors, there was a trend to increase with patient age (p=0.020 and p=0.025, respectively). On the contrary, the distribution of inflammatory aspects (p<0.001) and AAH (p=0.003) significantly varied according to prostate volume, and particularly in regards to chronic inflammation, there was a trend to increase depending on the prostate volume (p=0.002). Only the presence of T1b tumor but not of the other histological parameters associated to BPH, was able to significantly influence serum PSA. CONCLUSION In our analysis different histological variables associated to BPH are differently influenced by the age of patients and prostate volume, and they differently influence serum PSA levels.

Role of Dynamic Contrast-Enhanced Magnetic Resonance (MR) Imaging and Proton MR Spectroscopic Imaging in the Detection of Local Recurrence after Radical Prostatectomy for Prostate Cancer

OBJECTIVES To assess the accuracy of magnetic resonance (MR) spectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced MR (DCEMR) in the depiction of local prostate cancer recurrence in patients with biochemical progression after radical prostatectomy (RP). MATERIALS AND METHODS 1H-MRSI and DCEMR were performed in 70 patients at high risk of local recurrence after RP. The population was divided on the basis of the clinical validation of MR results with the use of a transrectal ultrasound biopsy examination in a group of 50 patients (group A) and the prostate-specific antigen (PSA) serum level restitution after external beam radiotherapy, in a group of 20 patients (group B). RESULTS In group A, 1H-MRSI analysis alone showed a sensitivity of 84% and a specificity of 88%; the DCEMR analysis alone, a sensitivity of 71% and a specificity of 94%; combined 1HMRSI-DCEMR, a sensitivity of 87% and specificity of 94%. Areas under the receiver operating characteristic (ROC) curve for 1HMRSI, DCEMR, and combined 1HMRSI /DCEMR were 0.942, 0.93,1 and 0.964, respectively. In group B, 1HMRSI alone showed a sensitivity of 71% and a specificity of 83%; DCEMR, a sensitivity of 79% and a specificity of 100%; combined 1HMRSI and DCEMR, a sensitivity of 86% and a specificity of 100%. Areas under the ROC curve for each of these groups were 0.81, 0.923, and 0.94, respectively. CONCLUSION Our results show that combined 1H-MRSI and DCMRE is an accurate method to identify local prostate cancer recurrence in patients with biochemical progression after RP.

Value of magnetic resonance spectroscopy imaging and dynamic contrast-enhanced imaging for detecting prostate cancer foci in men with prior negative biopsy

Purpose: This study aimed to prospectively analyze the role of magnetic resonance spectroscopy imaging (MRSI) and dynamic-contrast enhancement magnetic resonance (DCEMR) in the detection of prostate tumor foci in patients with persistently elevated prostate-specific antigen levels (in the range of ≥4 ng/mL to <10 ng/mL) and prior negative random trans-rectal ultrasound (TRUS)-guided biopsy. Experimental Design: This was a prospective randomized single-center study. One hundred and eighty eligible cases were included in the study. Patients in group A were submitted to a second random prostate biopsy, whereas patients in group B were submitted to a 1H-MRSI-DCEMR examination and samples targeted on suspicious areas were associated to the random biopsy. Results: At the second biopsy, a prostate adenocarcinoma histologic diagnosis was found in 22 of 90 cases (24.4%) in group A and in 41 of 90 cases (45.5%) in group B (P = 0.01). On a patient-by-patient basis, MRSI had 92.3% sensitivity, 88.2% specificity, 85.7% positive predictive value (PPV), 93.7% negative predictive value (NPV), and 90% accuracy; DCEMR had 84.6 % sensitivity, 82.3% specificity, 78.5% PPV, 87.5% NPV, and 83.3% accuracy; and the association MRSI plus DCEMR had 92.6% sensitivity, 88.8% specificity, 88.7% PPV, 92.7% NPV, and 90.7% accuracy, for predicting prostate cancer detection. Conclusions: The combination of MRSI and DCEMR showed the potential to guide biopsy to cancer foci in patients with previously negative TRUS biopsy. To avoid a potential bias, represented from having taken more samples in group B (mean of cores, 12.17) than in group A (10 cores), in the future a MRSI/DCEMR directed biopsy could be prospectively compared with a saturation biopsy procedure. Clin Cancer Res; 16(6); 1875–83

Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: A randomized study

OBJECTIVES To assess whether the proportion of men with clinically significant prostate cancer (PCa) is higher among men randomized to multiparametric magnetic resonance imaging (mp-MRI)/biopsy vs. those randomized to transrectal ultrasound (TRUS)-guided biopsy. METHODS In total, 1,140 patients with symptoms highly suggestive of PCa were enrolled and divided in 2 groups of 570 patients to follow 2 different diagnostic algorithms. Group A underwent a TRUS-guided random biopsy. Group B underwent an mp-MRI and a TRUS-guided targeted+random biopsy. The accuracy of mp-MRI in the diagnosis of PCa was calculated using prostatectomy as the standard of reference. RESULTS In group A, PCa was detected in 215 patients. The remaining 355 patients underwent an mp-MRI: the findings were positive in 208 and unremarkable in 147 patients. After the second random+targeted biopsy, PCa was detected in 186 of the 208 patients. In group B, 440 patients had positive findings on mp-MRI, and PCa was detected in 417 at first biopsy; 130 group B patients had unremarkable findings on both mp-MRI and biopsy. In the 130 group B patients with unremarkable findings on mp-MRI and biopsy, a PCa Gleason score of 6 or precancerous lesions were detected after saturation biopsy. mp-MRI showed an accuracy of 97% for the diagnosis of PCa. CONCLUSIONS The proportion of men with clinically significant PCa is higher among those randomized to mp-MRI/biopsy vs. those randomized to TRUS-guided biopsy; moreover, mp-MRI is a very reliable tool to identify patients to schedule in active surveillance.

Prostate cancer: 1HMRS-DCEMR at 3 T versus [(18)F]choline PET/CT in the detection of local prostate cancer recurrence in men with biochemical progression after radical retropubic prostatectomy (RRP)

OBJECTIVES This study compares proton magnetic resonancespectroscopic imaging (1H-MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) combined techniques at 3T magnet versus [(18)F]choline PET/computed tomography (CT) in the detection of local prostate cancer recurrence in patients with biochemical progression after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS 84 consecutive patients at high risk of local recurrence underwent combined 1HMRSI-DCEMR and 18-Fcholine- PET/CT. MR scan protocol included turbo spin echo (TSE) T2-weighted sequences in the axial, sagittal and coronal planes; three-dimensional (3D) chemical shift imaging (CSI) sequences with spectral/spatial pulses optimized for quantitative detection of choline and citrate; dynamic contrast enhanced gradient-echo (GRE) T1-weighted sequence. The population was divided into two groups. Group A included 28 patients with a lesion size ranging between 5.00mm and 7.2mm and PSA reduction following radiation therapy. Group B included 56 patients with a lesion size between 7.6mm and 19.4mm. Sensitivity, specificity, positive predictive value (PPV) and accuracy were evaluated and receiver operating characteristic (ROC) curves were performed. RESULTS In Group A combined 1H-MRSI and DCE-MRI showed a sensitivity of 92%, a specificity of 75% (PPV 96%) while PET-CT examination showed a sensitivity of 62% and a specificity of 50% (PPV 88%) in identifying local recurrence. The accuracy of MRI was 89% while PET-CT showed an accuracy of 60%. Areas under the ROC curve (AUC) values for MR and PET-CT were 0.833 and 0.562, respectively. In Group B combined 1H-MRSI and DCEMR showed a sensitivity of 94% and a specificity of 100% (PPV 100%) with accuracy of 94%. PET-CT had a sensitivity of 92% and a specificity of 33% (PPV 98%) with accuracy of 91%. The AUCs for MR and PET-CT values were 0.971 and 0.837, respectively. CONCLUSION The diagnostic accuracy of combined 1HMRSI-DCEMR was higher than PET/CT to identify local prostate cancer recurrence, mostly in patients with low biochemical progression after RRP (0.2-2ng/mL).

Early Recovery of Urinary Continence After Radical Prostatectomy Using Early Pelvic Floor Electrical Stimulation and Biofeedback Associated Treatment

PURPOSE We analyzed the benefit of the early combined use of functional pelvic floor electrical stimulation and biofeedback in terms of time to recovery and rate of continence after radical prostatectomy. MATERIALS AND METHODS A total of 60 consecutive patients who underwent radical prostatectomy were included in the study. Patients were prospectively randomized to a treatment group (group 1) vs a control group (group 2). In group 1 a program of pelvic floor electrical stimulation plus biofeedback began 7 days after catheter removal, twice a week for 6 weeks. Each of the 12 treatment sessions was composed of biofeedback (15 minutes) followed by pelvic floor electrical stimulation (20 minutes). The evaluation of continence was performed at time 0, at 2 and 4 weeks, and at 2, 3, 4, 5 and 6 months during followup. Evaluations were performed using the 24-hour pad test and the incontinence section of the International Continence Society questionnaire. RESULTS The mean leakage weight became significantly lower (p <0.05) in group 1 than in group 2 starting at 4 weeks until 6 months of followup. A significant difference (p <0.05) between groups 1 and 2 in terms of percentage of continent patients was achieved from 4 weeks (63.3% group 1 and 30.0% group 2) to 6 months (96.7% group 1 and 66.7% group 2). CONCLUSIONS Early, noninvasive physical treatment with biofeedback and pelvic floor electrical stimulation has a significant positive impact on the early recovery of urinary continence after radical prostatectomy.

Prognostic value of circulating tumor cells in nonmuscle invasive bladder cancer: a CellSearch analysis

BACKGROUND Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. RESULTS CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P < 0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. CONCLUSION The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.BACKGROUND Circulating tumor cells (CTCs) provide prognostic information in patients with metastatic tumors. Recent studies have shown that CTCs are released in circulation in an early phase of cancer disease so that their presence is under investigation in the adjuvant setting. Few studies investigated the prognostic significance of CTCs enumeration in patients with metastatic and advanced bladder cancer. The current study has analyzed the presence of CTC in patients with nonmuscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS Forty-four NMIBC patients were enrolled and included in a 24-month follow-up program. Blood drawings were carried out in all patients at the first diagnosis. CellSearch system (Veridex; LLC, Raritan, NJ) was used for CTCs enumeration. RESULTS CTC were detectable in 8/44 patients (18%). Presence of CTC was found significantly associated to shorter time to first recurrence (6.5 versus 21.7 months, P<0.001). Median time to progression was not reached, due to the short follow-up period. CTC presence was found associated to concomitant carcinoma in situ and higher T category. CONCLUSION The detection of CTC in this setting of disease may allow to distinguish patients with high risk of recurrence from those with high risk of progression, as well as to early identify patients candidate for adjuvant treatment.

Neuroendocrine differentiation in human prostate tissue: is it detectable and treatable?

which is present in the normal, hyperplastic and dysplastic prostate. NE cells are located in all regions of the human prostate at birth, but rapidly decrease in the peripheral prostate after birth and then reappear at puberty [4]. After puberty, the number of NE cells seems to increase until an apparently optimum level is reached, which persists from 25 to 54 years old [5]. The relationship of age beyond puberty to the number and distribution of these endocrine-paracrine cells has not been definitively assessed, but in the guinea pig these cells in the peripheral prostate increase markedly with adult age [6]. Studies on adult human prostates indicate that NE cells are more frequent in the periurethral ducts than in the peripheral parts of the gland [7]. Others [8,9] also described the presence of NE cells in the stroma of fetal and infantile prostates.

Circulating tumor cells detection has independent prognostic impact in high-risk non-muscle invasive bladder cancer

High‐risk non‐muscle invasive bladder cancer (NMIBC) progresses to metastatic disease in 10–15% of cases, suggesting that micrometastases may be present at first diagnosis. The prediction of risks of progression relies upon EORTC scoring systems, based on clinical and pathological parameters, which do not accurately identify which patients will progress. Aim of the study was to investigate whether the presence of CTC may improve prognostication in a large population of patients with Stage I bladder cancer who were all candidate to conservative surgery. A prospective single center trial was designed to correlate the presence of CTC to local recurrence and progression of disease in high‐risk T1G3 bladder cancer. One hundred two patients were found eligible, all candidate to transurethral resection of the tumor followed by endovesical adjuvant immunotherapy with BCG. Median follow‐up was 24.3 months (minimum–maximum: 4–36). The FDA‐approved CellSearch System was used to enumerate CTC. Kaplan–Meier methods, log‐rank test and multivariable Cox proportional hazard analysis was applied to establish the association of circulating tumor cells with time to first recurrence (TFR) and progression‐free survival. CTC were detected in 20% of patients and predicted both decreased TFR (log‐rank p < 0.001; multivariable adjusted hazard ratio [HR] 2.92 [95% confidence interval: 1.38–6.18], p = 0.005), and time to progression (log‐rank p < 0.001; HR 7.17 [1.89–27.21], p = 0.004). The present findings provide evidence that CTC analyses can identify patients with Stage I bladder cancer who have already a systemic disease at diagnosis and might, therefore, potentially benefit from systemic treatment.

Premature ejaculation results in female sexual distress: standardization and validation of a new diagnostic tool for sexual distress.

PURPOSE We measured premature ejaculation related female sexual distress using a new diagnostic tool, the Female Sexual Distress Scale-Revised-Premature Ejaculation questionnaire. MATERIALS AND METHODS In this large-scale, Internet based population study we evaluated 2,109 women in a stable relationship during the last 6 months. The 1,361 women in the premature ejaculation group had no female sexual disorder but the partner had premature ejaculation alone. The 748 controls had no female sexual disorder and a partner without premature ejaculation. We determined questionnaire content and discriminant validity, internal consistency and test-retest reliability. Multivariate logistic regression with propensity score reweighting was done to determine the clinical impact of demographics on the perception of sexual distress. RESULTS The questionnaire was well understood. Internal consistency was greater than 0.90 and 0.84 in the premature ejaculation and control groups, respectively. Test-retest reliability was 0.82 (95% CI 0.72-0.87) and 0.85 (95% CI 0.79-0.92) in the premature ejaculation and control groups, respectively. The questionnaire had a high AUC of 0.90 (95% CI 0.89-0.91). The new cutoff score of 12 or greater had 79.1% sensitivity (95% CI 73.8-82.5), 99.5% specificity (95% CI 98.0-100.0), 99.3% positive predictive value (95% CI 98.7-100.0) and 67.9% negative predictive value (95% CI 64.2-73.2). Median questionnaire scores were significantly higher in the premature ejaculation group than in controls (20, 95% CI 19-21 vs 6, 95% CI 6-7, p <0.0001). Logistic regression adjusted and unadjusted by propensity score indicated that women in the premature ejaculation group had a 7.12 (95% CI 5.98-10.14, p <0.0001) to 9.83 (95% CI 7.94-12.15) greater probability of sexual distress than controls. CONCLUSIONS The Female Sexual Distress Scale-Revised-Premature Ejaculation questionnaire fulfills psychometric requirements for measuring sexual distress related to partner sexual dysfunction.