Lucio Miano

Ultrasound assessment of intravesical prostatic protrusion and detrusor wall thickness--new standards for noninvasive bladder outlet obstruction diagnosis?

PURPOSE We evaluated the accuracy of detrusor wall thickness and intravesical prostatic protrusion, and the association of each test to diagnose bladder prostatic obstruction in patients with lower urinary tract symptoms. MATERIALS AND METHODS We enrolled in the study 100 consecutive patients with lower urinary tract symptoms due to benign prostatic hyperplasia. Baseline parameters were International Prostate Symptom Score, prostate volume, urinary flow rate, intravesical prostatic protrusion, detrusor wall thickness, Schaefer obstruction class, minimal urethral opening pressure and the urethral resistance algorithm bladder outlet obstruction index. A ROC curve was produced to calculate AUC and evaluate the diagnostic performance of intravesical prostatic protrusion, detrusor wall thickness and prostate volume for bladder prostatic obstruction. RESULTS We noted a highly significant correlation between intravesical prostatic protrusion and the bladder outlet obstruction index (Spearmans rho = 0.49, p = 0.001), and Schaefer obstruction class (Spearmans rho = 0.51, p = 0.001). A highly significant correlation was also observed for detrusor wall thickness and the bladder outlet obstruction index (Spearmans rho = 0.57, p = 0.001), detrusor wall thickness and Schaefer obstruction class (Spearmans rho = 0.432, p = 0.02). On multivariate analysis intravesical prostatic protrusion and detrusor wall thickness were the only parameters associated with bladder prostatic obstruction (p = 0.015). The AUC for intravesical prostatic protrusion was 0.835 (95% CI 0.756-0.915) and for detrusor wall thickness it was 0.845 (95% CI 0.78-0.91). The association of intravesical prostatic protrusion and detrusor wall thickness produced the best diagnostic accuracy (87%) when the 2 tests were done consecutively. CONCLUSIONS Suprapubic ultrasound of detrusor wall thickness and intravesical prostatic protrusion is a simple, noninvasive, accurate system to assess bladder prostatic obstruction in patients with lower urinary tract symptoms due to benign prostatic hyperplasia.

Oxidative Stress in Benign Prostatic Hyperplasia and Prostate Cancer

Objective: The aim was to verify whether oxidative stress could represent a common key factor of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Subjects and Methods: 15 patients affected by BPH, 15 with PCa and 15 controls were enrolled. Blood samples were withdrawn systemically and locally during radical retropubic prostatectomy in patients with PCa and during transvesical retropubic adenomectomy in patients diagnosed with BPH. Plasma oxidized low-density lipoprotein, peroxides, and total equivalent antioxidant capacity (TEAC) including plasma superoxide dismutase (SOD) determination were analyzed as oxidative markers. Results: With respect to the control group, high plasma peroxides and decreased TEAC levels were measured in patients affected by both PCa and BPH. Plasma peroxides were significantly higher in patients with PCa with respect to BPH. A positive correlation was found between peroxides and TEAC values in samples withdrawn locally in patients affected by PCa. An inverse correlation between peroxides and TEAC was observed in patients with BPH. No statistically significant modifications were observed as concerns SOD activity and LDL oxidability. Conclusions: Our findings confirm a significant unbalance of redox status in patients affected by BPH and PCa, and suggest a potential involvement of oxidative stress as a determinant in the pathogenesis of these diseases.

Abdominal obesity as risk factor for prostate cancer diagnosis and high grade disease: A prospective multicenter Italian cohort study

OBJECTIVE To evaluate the association between abdominal obesity and prostate cancer (CaP) diagnosis and grade in patients undergoing prostate biopsy. MATERIALS AND METHODS Between 2008 and 2011, we prospectively enrolled patients referred to 3 clinics in Italy who were scheduled for transrectal ultrasound (TRUS) guided prostate biopsy. Before biopsy, digital rectal examination (DRE), prostate specific antigen (PSA), body mass index (BMI), and waist circumference (WC) were measured. Men were categorized in 4 groups of body habitus, according to BMI and waist circumference values. Crude and adjusted logistic regressions were performed to assess the association of BMI (continuous), waist circumference (continuous), body habitus (categorical), and CaP diagnosis and grade. RESULTS Six hundred sixty-eight patients were enrolled. CaP was detected in 246 patients (38%), of whom 136 had low-grade (Gleason score ≤ 6) and 110 high-grade cancer (Gleason score ≥ 7). Logistic regression multivariate analysis showed that BMI (OR 1.05 per unit, CI 95% 1.00-1.10 P = 0.033) and waist circumference (OR 1.02 per cm, CI 95% 1.00-1.04 P = 0.026) were significant predictors of CaP diagnosis. BMI (OR 1.11 95% CI 1.04-1.18 P = 0.001) and WC (OR 1.04 95% CI 1.02-1.06 P = 0.001) were also associated with high-grade CaP. Furthermore, obesity with central adiposity (BMI ≥ 30 kg/m(2) and WC ≥ 102 cm) was significantly associated with CaP diagnosis (OR 1.66, CI 95% 1.05-2.63, P = 0.03) and high-grade disease (OR 2.56, CI 95% 1.38-4.76, P = 0.003). CONCLUSIONS Obesity defined by BMI and WC seems to be associated with CaP and, more specifically, with high-grade disease at the time of biopsy. The relationship between obesity and CaP is complex and remains to be further addressed.

Local Anesthesia Reduces Pain Associated with Transrectal Prostatic Biopsy

Introduction: To test the hypothesis that periprostatic block could completely relief prostatic biopsy-associated pain. Materials and Methods: Patients scheduled for transrectal ultrasound guided prostate biopsy were randomized (1:1:1 ratio) to no analgesia (group A), endorectal enema of 1% lidocaine gel (group B) or transrectal periprostatic block (group C). All patients underwent 10 core TRUS-guided biopsy. After the procedure, a ten visual analogue pain score (VAS) from 0 = no discomfort to 10 = severe pain was administered to the biopsied patients and a global estimation of pain associated with the procedure was obtained. The study design included interim analysis of pain score after the first 60 patients were enrolled. Kruskal-Wallis test for unpaired data was used for statistical analysis. Data are presented as mean, median (range). Results: Sixty patients were enrolled between May 2003 and December 2003 and all patients were evaluable. Mean and median age was 68.5 and 69 (range 53–82) years, respectively. Mean and median PSA was 86.8 and 9 ng/ml (range 0.58–4.111), respectively. No major side effects were observed. Patients in group A scored at VAS a median 4, mean 5.5 ± 2.3 (range 3–10). Patients in group B scored a median 4, mean 5.5 ± 2.7 (range 3–10) (p = 0.237). Patients receiving periprostatic injections of carbocaine (group C) scored a median 0, mean 0.5 ± 0.8 (range 0–2). The level of pain reported by this group of patients was significantly different from those reported by patients who performed prostatic biopsy without anesthesia or with intrarectal anesthetic jelly (p = 0.00001). In the periprostatic block group 65% of patients referred no pain after the procedure (VAS = 0) while all patients in the other groups experience some degree of pain. Conclusion: The use of bilateral periprostatic block is a very effective and useful technique, well tolerated by the patient, which almost completely abolishes the pain and discomfort associated with the prostatic biopsy procedure.

Invasive and Minimally Invasive Treatment Modalities for Lower Urinary Tract Symptoms: What Are the Relevant Differences in Randomised Controlled Trials?

Objectives: This manuscript reviews the outcomes of invasive and minimally-invasive treatments of lower urinary tract symptoms due to prostatic enlargement. Methods: The MEDLINE database was searched for Medical Subject headings and text words including prostatic hyperplasia, treatment, surgery, thermal treatments, thermotherapy, laser, TUNA and vaportrode. Data from both randomised and non-randomised controlled trials were considered. Results: All invasive treatments produce significant changes of all subjective and objective outcome parameters. The best clinical outcome has been reported for open prostatectomy followed by transurethral resection of the prostate. Complications of the different invasive techniques were difficult to analyse because of the heterogeneity of categories among different papers and lack of standard criteria. The major attraction of all minimally invasive treatment options is the low risk of bleeding requiring blood transfusions. Retrograde ejaculation was one of the most frequently reported complications for all invasive techniques. Some of the so-called less invasive treatment options appeared to be associated with a rather high incidence of minor complications somehow contradicting their minimally invasiveness. Re-treatment rate observed in patients receiving various minimally invasive treatments was always higher than following standard treatment options such as transurethral resection. Conclusions: Open prostatectomy and transurethral resection of the prostate outperform all minimally invasive treatment modalities as regards efficacy and durability of outcome. The lack of standard criteria to evaluate complications and side effects makes treatment comparisons difficult. Endorsement of the clinical research criteria proposed by the last WHO-sponsored International Consultation on BPH is strongly recommended to improve the clinical value of randomised and non-randomised controlled trials. More information is needed on long-term complications and cost-effectiveness of minimally invasive treatment modalities.

Continuous intra-arterial administration of recombinant interleukin-2 in low-stage bladder cancer. A phase IB study.

Toxicity and clinical effects of intra‐arterial (IA) continuous infusion of recombinant interleukin‐2 (rIL‐2) were evaluated in twelve patients with low‐stage transitional cell carcinoma (TCC) of the bladder (T1NOMO; G1 to G2). rIL‐2 dosages were escalated from 18 × 103 to 18 × 106 IU/m2/d in four groups of three patients. After two 5‐day courses, separated by a 48‐hour interval, evaluation of clinical response and transurethral resection (TUR) were carried out. World Health Organization (WHO) Grade 3 toxicity occurred in 2 of 12 patients (hypotension/mental confusion and fever, respectively); all side effects rapidly disappeared after infusion was abandoned. No laboratory toxicity developed in any patient. Two pathologically proven complete responses (CR) were achieved using 18 × 104 IU/m2/d, and three partial responses (PR) were achieved using 18 × 105 IU/m2/d in two patients and 18 × 106 IU/m2/d in one patient, giving an overall response rate of 42%. All objective responses are still ongoing after a mean follow‐up time of 23 months (range, 12 to 32 months). Local relapses occurred 3 months after TUR only in two nonresponders.

Photoselective Prostatic Vaporization for Bladder Outlet Obstruction: 12-Month Evaluation of Storage and Voiding Symptoms

PURPOSE We evaluated voiding and storage symptom evolution in patients treated with prostate photoselective vaporization by a KTP laser. MATERIALS AND METHODS Enrolled in the study were 150 consecutive patients with lower urinary tract symptoms due to benign prostatic hyperplasia and a diagnosis of bladder outlet obstruction. Patients underwent prostate photoselective vaporization with the 80 W KTP laser. Baseline parameters included prostate volume, International Prostate Symptom Score with voiding and storage symptom subscores, uroflowmetry, pressure flow study and serum prostate specific antigen. Patients were followed 1, 3, 6 and 12 months after surgery. RESULTS Mean +/- SD patient age was 69.6 +/- 10 years. Mean prostate volume was 52 +/- 18 ml. Mean International Prostate Symptom Score was 22.3 +/- 4, mean maximum urine flow was 9 +/- 2.9 ml per second and mean Schäfer obstruction class was 3.6 +/- 1. An average of 190 +/- 44 kJ were delivered in a mean of 68 +/- 24 minutes with an average of 3.6 kJ/ml prostate. The mean number of fibers was 1.2 +/- 0.4. Mean catheterization time was 20 +/- 8 hours. Retrograde ejaculation was reported in 67% of patients. Prostate specific antigen was significantly decreased at 12 months (2.6 +/- 2.3 vs 0.9 +/- 0.7 ng/ml, p = 0.001). Storage symptoms decreased by 54.5%, 63.6%, 72.7% and 81.8% at 1, 3, 6 and 12 months, respectively (p <0.001). Voiding symptoms decreased 63.6%, 72.7%, 81.8% and 90.9% at 1, 3, 6 and 12 months, respectively (p <0.001). CONCLUSIONS As shown by a prostate specific antigen significant decrease, proper prostate debulking may be achieved by prostate photoselective vaporization. Significant continuous improvement in storage and voiding symptoms was observed at up to 12-month followup.

Managing the Consequences of Obstruction

Abstract Nowadays, it is widely accepted that bladder outflow obstruction (BOO) is not the only cause of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), the aetiology is multifactorial. It is increasingly recognised that the bladder as well as the central and peripheral nervous system may be directly involved in the development of LUTS. This review focuses on the consequences of BOO for the bladder. As a response to obstruction, the bladder compensates for the progressive increase of pressure overload with detrusor hypertrophy. Initially, this response is sufficient to maintain detrusor contractility and bladder emptying, but sustained obstruction may finally induce (irreversible) bladder damage with subsequent risk of detrusor failure. It is therefore important, in the treatment of LUTS/BOO, not only to relieve LUTS, but also to prevent or reduce alterations in the bladder, such as the development of smooth muscle cells hyperplasia, collagen deposition, detrusor ischaemia and reperfusion injury. Limited data are currently available that evaluate the effect of LUTS/BPH therapies on disease progression at the bladder level. Reduction of the bladder mass has been observed following BPH surgery, confirming the results obtained following the relief of experimental obstruction in the rabbit and mini-pig models. Preliminary clinical data suggest a similar effect of the α 1 -adrenoceptor (AR) antagonist tamsulosin in BPH patients. In the management of LUTS/BPH, it is no longer sufficient to focus treatment on the prostate, but protection of bladder function has also become an important target for treatment. Patients should be treated soon enough to prevent the effect of BOO on the bladder and to lower the risk of BPH adverse events. The question remains as to when treatment should be initiated and for how long it should be maintained to prevent permanent bladder damage. This makes the pharmacological treatment of obstruction and its consequences a fascinating new approach in the management of LUTS/BPH patients.

The Electromagnetic Detection of Prostatic Cancer: Evaluation of Diagnostic Accuracy

OBJECTIVES To evaluate the accuracy of the TRIMprob in the diagnosis of prostate neoplasm. METHODS Consecutive patients referred for prostate biopsy were prospectively enrolled. Patients had history taken, physical examination by digital rectal examination (DRE) of the prostate, assessment of total and free serum prostate-specific antigen (PSA) levels, prostate transrectal ultrasonography (TRUS), and TRIMprob test. Indications for prostate biopsy included one or more of the following conditions: total serum PSA levels of 4.0 ng/mL or more, free/total serum PSA ratio of 0.18 or less, positive results on DRE, and suspicious findings on TRUS. Twelve-core, TRUS-guided biopsies were performed with local anesthesia. A blinded investigator performed the TRIMprob test; the lowest value of the signal at 465 MHz was looked for and recorded, although data of the electromagnetic signal at 930 and 1295 MHz were also recorded. RESULTS One hundred eleven patients (aged 64.9 +/- 8.1 years, mean +/- standard deviation), enrolled between November 2004 and August 2005, were analyzed. Total serum PSA level was 8.4 +/- 3.6 ng/mL, and free/total serum PSA ratio was 0.15 +/- 0.7. TRIMprob sensitivity for the diagnosis of prostate cancer was 0.86%; specificity and positive and negative predictive values were 0.60 and 0.88; accuracy was 72%. TRIMprob accuracy outperformed any other diagnostic parameter considered, including the rule of chance. The association of TRIMprob and DRE offered a sensitivity and a negative predictive value of 0.86% or greater. CONCLUSIONS TRIMprob had the highest accuracy rate, among all other tests, for the diagnosis of prostate cancer. Electromagnetic detection with the TRIMprob test seems to be a promising technology and a useful additional tool for the early detection of prostate cancer.

Early diagnosis of prostatic carcinoma based on in vitro culture of viable tumor cells harvested by prostatic massage.

Prostatic cancer is diagnosed too late in most cases, so that therapy is frequently ineffective or even not undertaken at all because of the already advanced stage of the disease. An early diagnosis technique for prostatic cancer would therefore be highly desirable, also because all other available markers give very unsatisfactory results. Because of our experience in tissue culture of human prostatic specimens, by which we have shown good correlations with patient prognosis, we attempted to grow epithelial cells collected from prostatic fluid after rectal prostatic massage. Samples from prostatic cancer patients, diagnosed by needle biopsy, were grown in culture and were able to survive in vitro for at least 2 weeks, thus providing morphological and biochemical data concerning their neoplastic and differentiation features. The early data on this new approach, which we believe might represent a very useful test for the early diagnosis of the neoplasm, are reported here. The method is noninvasive and suitable for mass screening of the disease. Accuracy and reliability of the technique are currently being tested.