Giorgio Franco

The evolution of detrusor overactivity after watchful waiting, medical therapy and surgery in patients with bladder outlet obstruction.

PURPOSE We analyzed the evolution of detrusor overactivity in patients with bladder outlet obstruction treated with either medical or surgical therapy or watchful waiting. MATERIALS AND METHODS Of 255 patients with symptomatic benign prostatic enlargement who completed the International Prostate Symptom Score and underwent full urodynamic investigation 161 presented with bladder outlet obstruction. Of the 161 men 101 were reevaluated with a second clinical evaluation and urodynamics 1 to 5 years (mean 2) after watchful waiting in 20, medical treatment (alfuzosin 20 and finasteride 16) in 36 and surgery (transurethral incision of the prostate 13 and prostatectomy 32) in 45. For statistical analysis Wilcoxon matched paired data and Kruskal Wallis tests were used as appropriate. RESULTS Overall detrusor overactivity was present in 53 patients (52%) at baseline and 41 (40%) at followup. Detrusor overactivity was present in 9 patients (45%) at baseline and 11 (55%) at followup in the watchful waiting group (p = 0.17); 7 (35%) at baseline and 6 (30%) at followup in the alfuzosin group (p = 0.37); 10 (62.5%) at baseline and 10 at followup in the finasteride group (p = 1); 6 (46%) at baseline and 4 (30%) at followup in the transurethral prostate incision group (p = 0.48); and 21 (68%) at baseline and 10 (31%) at followup in the prostatectomy group (p = 0.02). CONCLUSIONS Detrusor overactivity is highly prevalent (52%) in patients with bladder outlet obstruction, and appears to persist for long periods when obstruction is left untreated or treated only with medical therapy. However, surgical treatment of bladder outlet obstruction, prostatectomy in particular, significantly reduces the incidence of detrusor overactivity and lessens the chance of its de novo appearance for up to 5 years.

Expression and Cellular Localization of Follicle-Stimulating Hormone Receptor in Normal Human Prostate, Benign Prostatic Hyperplasia and Prostate Cancer

PURPOSE FSH, identified as an endogenous product of the prostate, is a glycoprotein with proliferative activity. Increasing evidence of autocrine/paracrine activities of gonadotropins at extragonadal sites led us to investigate the gene expression and cellular localization of FSH-R in normal and diseased human prostates. MATERIALS AND METHODS Prostate specimens, including normal gland, BPH, PCa and human androgen refractory (PC3) and androgen dependent (LNCaP) prostate cancer cell lines (European Collection of Cell Cultures, Salisbury, United Kingdom), were analyzed for FSH-R expression by semiquantitative and real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. We also evaluated cyclic adenosine monophosphate production by cultured PC3 and LNCaP stimulated with human FSH. RESULTS Little FSH-R expression was seen in 9 of 13 normal and 8 of 15 BPH specimens. Of 30 PCa samples 21 were FSH-R positive with generally higher expression compared to normal prostate and BPH samples. Real-time reverse transcriptase-polymerase chain reaction of matched normal/tumor pairs confirmed higher FSH-R mRNA expression in PCa. PC3 cells expressed FSH-R, while LNCaP cells were FSH-R negative. FSH-R protein was mainly localized in the glandular epithelium and in some stromal cells in normal prostate, BPH and PCa specimens. PC3 cells expressed FSH-R protein and their treatment with FSH induced a significant increase in cyclic adenosine monophosphate production. CONCLUSIONS These results indicate that a subset of PCa expresses FSH-R mRNA and protein at levels higher than those of normal and hyperplastic tissues that express FSH-R. This suggests that FSH might contribute to some cases of PCa via a receptor mediated mechanism.

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.

Analysis of radical cystectomy and urinary diversion complications with the Clavien classification system in an Italian real life cohort

INTRODUCTION Standardized methods of reporting complications after radical cystectomy (RC) and urinary diversions (UD) are necessary to evaluate the morbidity associated with this operation to evaluate the modified Clavien classification system (CCS) in grading perioperative complications of RC and UD in a real life cohort of patients with bladder cancer. MATERIALS AND METHODS A consecutive series of patients treated with RC and UD from April 2011 to March 2012 at 19 centers in Italy was evaluated. Complications were recorded according to the modified CCS. Results were presented as complication rates per grade. Univariate and binary logistic regression analysis were used for statistical analysis. RESULTS RESULTS AND LIMITATIONS 467 patients were enrolled. Median age was 70 years (range 35-89). UD consisted in orthotopic neobladder in 112 patients, ileal conduit in 217 patients and cutaneous ureterostomy in 138 patients. 415 complications were observed in 302 patients and were classified as Clavien type I (109 patients) or II (220 patients); Clavien type IIIa (45 patients), IIIb (22 patients); IV (11 patients) and V (8 patients). Patients with cutaneous ureterostomy presented a lower rate (8%) of CCS type ≥IIIa (p = 0.03). A longer operative time was an independent risk factor of CCS ≥III (OR: 1.005; CI: 1.002-1.007 per minute; p = 0.0001). CONCLUSIONS In our study, RC is associated with a significant morbidity (65%) and a reduced mortality (1.7%) when compared to previous experiences. The modified CCS represents an easily applicable tool to classify the complications of RC and UD in a more objective and detailed way.

Bipolar Transurethral Resection of Prostate: Clinical and Urodynamic Evaluation

OBJECTIVES To report our experience with the clinical effectiveness of endoscopic resection of the prostate using the bipolar Gyrus PlasmaKinetic System. METHODS A total of 120 patients with lower urinary tract symptoms were observed from 2002 to 2005. Of these 120 patients, 90 developed benign prostatic hyperplasia and were considered to have obstruction, and 51 of these 90 were scheduled for prostate surgery. The patients were randomized 1:1, using envelopes, into two groups: bipolar transurethral resection of the prostate (TURP) using the Gyrus PlasmaKinetic System (PK group) and monopolar TURP (standard TURP group). All patients were evaluated at baseline and follow-up (12 months after treatment) by medical history, International Prostate Symptom Score, inclusive of the question on quality of life, and physical examination, including digital rectal examination, transrectal ultrasonography, and pressure flow study. Statistical analysis was applied on the change in International Prostate Symptom Score and urodynamic parameters comparing the endpoints with baseline and comparing the baseline and follow-up characteristics between the two groups. RESULTS The mean resection time was 39.1 minutes and 31.7 minutes for the PK and standard TURP groups, respectively (P = 0.437). The mean postoperative hemoglobin reduction at 24 hours of follow-up was 1.25 g/dL, with a 2.1% hematocrit reduction, in the PK group and 1.81 g/dL, with a 3.2% hematocrit reduction, in the standard TURP group (P = 0.716). Improvements in flow rate, International Prostate Symptom Score, quality-of-life score, and bladder outlet obstruction grade were comparable between the two groups. CONCLUSIONS Bipolar TURP using the bipolar Gyrus PlasmaKinetic System seems to be a safe and effective procedure that is potentially associated with fewer side effects and could result in this procedure being more attractive for high-risk patients or, as recently proposed, for training purposes.

Conservative treatment of intraperitoneal bladder perforation during transurethral resection of bladder tumor.

A new technique for conservative treatment of intraperitoneal bladder perforation during transurethral resection of bladder tumor is presented. This technique consists in the percutaneous insertion of an intraperitoneal drainage tube, using as a guide the sheath of the resectoscope, which is advanced through the bladder perforation and peritoneum up to the abdominal wall.

Birth of 16 healthy children after ICSI in cases of nonmosaic Klinefelter syndrome

STUDY QUESTION Does the health status of infants fathered by nonmosaic Klinefelter syndrome (KS) patients whose partners underwent ICSI with sperm obtained from testicular dissection reveal any genetic risk for the offspring?. SUMMARY ANSWER KS patients undergoing testicular sperm extraction (TESE) are capable of conceiving healthy children. WHAT IS KNOWN ALREADY Paternity has been successfully achieved in nonmosaic KS patients (47,XXY karyotype) by ICSI using either ejaculated or testicular spermatozoa. A crucial concern is the potential transmission of genetic abnormalities to the offspring. Some studies reported that 47,XXY spermatogonia are capable of completing spermatogenesis leading to the production of mature spermatozoa with increased aneuploidies. Other authors showed that where focal spermatogenesis is present in nonmosaic KS males, it originates from euploid germ cells and, therefore, produces normal mature gametes. In support of this finding, at present, the great majority of children born from nonmosaic KS patients are chromosomally normal. STUDY DESIGN, SIZE, DURATION From April 2004 to June 2010, 38 azoospermic patients with nonmosaic KS were examined for the presence of testicular spermatozoa. Spermatozoa were retrieved from 15 patients and 26 ICSI cycles were done (16 with cryopreserved sperm). There were 15 pregnancies leading to the birth of 16 babies who were karyotyped at amniocentesis and after birth. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were recruited from couples attending the European Hospital, Rome, and Clinica MAR&Gen, Granada, for infertility treatment. Both the European Hospital and Clinica MAR&Gen are private clinics. Testicular tissue was extracted with TESE or micro-TESE. After retrieval, fresh sperm was used for ICSI or it was cryopreserved for future use. MAIN RESULTS AND THE ROLE OF CHANCE Spermatozoa were retrieved from 15 patients (14 TESE and 1 micro-TESE) out of 38 (39.5%). A total of 26 ICSI cycles were performed: 10 with fresh and 16 with cryopreserved-thawed sperm. Mean ages (y) of patients with positive and negative sperm retrieval were, respectively, 34.8 ± 1.72 and 35.6 ± 4.08 (NS, nonsignificant). Comparing ICSI cycles performed with fresh sperm (n = 10) to those performed with frozen-thawed sperm (n = 16): Fertilization rates per injected oocyte were 53.0% (44 of 83) and 47.8% (32 of 67), respectively (NS). The cleavage rate per injected oocyte was 90.6% (29 of 32) versus 68.2% (30 of 44); P = 0.026. Clinical outcomes were not significantly different between the fresh and the frozen-thawed sperm group: clinical pregnancy rates were 7 of 10 (70.0%) and 8 of 16 (50.0%); implanted embryos (per transferred embryo) were 8 of 23 (34.8%) and 8 of 29 (27.6%); delivery rates were 6 of 10 (60.0%) and 5 of 16 (31.3%). Sixteen babies were born, all of them are healthy with a normal karyotype, eight from the fresh sperm group and eight from the frozen-thawed sperm group. LIMITATIONS, REASONS FOR CAUTIONS The small numbers available for study mean that only common problems can be excluded. WIDER IMPLICATIONS OF THE FINDINGS This study provides further reassurance that KS men can father healthy children and that pre-implantation genetic diagnosis on embryos conceived with their sperm is not strongly indicated. However, until conclusive information is available, such couples should be offered extensive genetic counseling. STUDY FUNDING/COMPETING INTEREST(S) No external funding was obtained for the present study. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.

Differential Diagnosis of Nonpalpable Testicular Lesions: Qualitative and Quantitative Contrast-enhanced US of Benign and Malignant Testicular Tumors

PURPOSE To evaluate the diagnostic accuracy of unenhanced and quantitative contrast-enhanced ultrasonography (US) in the differential diagnosis of small nonpalpable testicular lesions. MATERIALS AND METHODS The local review board approved the protocol, and all patients provided written informed consent. One hundred fifteen patients (median age, 34 years; age range, 14-61 years) with nonpalpable testicular lesions were consecutively enrolled between 2006 and 2012 and underwent unenhanced scrotal US, contrast-enhanced US, surgical enucleation, and at least 18 months of follow-up. Clinical and histologic features were recorded, and qualitative and quantitative analysis of contrast-enhanced US time-intensity curves were performed. Logistic regression analysis was performed to explore features of malignancy. Receiver operating characteristic ( ROC receiver operating characteristic ) curves were developed for cumulative unenhanced and contrast-enhanced US scores. RESULTS All lesions were 1.5 cm or smaller. Forty-four of the 115 patients (38%) had malignant tumors, 42 had benign tumors (37%), and 29 (25%) had nonneoplastic lesions. The features at unenhanced US that enabled the best differentiation of tumors versus nonneoplastic lesions and benign versus malignant tumors were parenchymal microlithiasis (26 of 86 patients with tumors vs five of 29 patients with nonneoplastic lesions [P = .178]; four of 42 patients with benign lesions vs 22 of 44 patients with malignant tumors [P < .001]), irregular margins (26 of 86 patients with tumors vs three of 29 patients with nonneoplastic lesions [P < .001]; eight of 42 patients with benign lesions vs 18 of 44 patients with malignant tumors [P < .001]), and internal vascularization (70 of 86 patients with tumors vs seven of 29 patients with nonneoplastic lesions [P < .001]; 28 of 42 patients with benign lesions vs 42 of 44 patients with malignant tumors [P < .001]). For contrast-enhanced US, the rapidity of wash-in (34 of 44 patients vs 15 of 42 patients, P < .001) and washout (33 of 44 patients vs five of 42 patients, P < .001) were the parameters that best differentiated malignant from benign tumors, with a typical prolonged washout observed in Leydig cell tumors (12 of 21 patients, P < .001 when compared with seminomas). Overall, the combination of unenhanced and contrast-enhanced US achieved a high accuracy in the diagnosis of small testicular malignancies (area under the ROC receiver operating characteristic curve performance: 0.927; 95% confidence interval: 0.872, 0.981). CONCLUSION Benign testicular tumors are frequent incidental findings. Quantitative scrotal contrast-enhanced US is a noninvasive diagnostic tool that could improve the differential diagnosis and individualized management of small testicular lesions.

Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy

Salvage radical prostatectomy is considered for patients with locally recurrent prostate cancer after external beam radiotherapy. Between 2001 and 2004, 32 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. We assessed the morbidity associated with this procedure and the outcome of the patients. Thirty‐two patients underwent salvage radical prostatectomy. Initial pre‐radiation median prostate‐specific antigen was 13 ng/ml. Pre‐radiation disease was clinical stage T1b in five cases, T2a in 10, T2b in 10 and T3a in seven. Mean operative time was 122 minutes, intraoperative blood loss was 550 ml and hospital stay and catheterization time were 5 and 12 days, respectively. There was biochemical failure in eight patients after salvage radical prostatectomy and 24 patients are biochemical non evidence of disease (bNED). In recurrent prostate local disease with prostate‐specific antigen <10 ng/ml and life expectancy greater than 10 years, salvage radical prostatectomy is a reasonable treatment option.

Long-term maintenance bacille Calmette-Guérin therapy in high-grade superficial bladder cancer.

OBJECTIVES To assess the long-term results of intravesical bacille Calmette-Guérin (BCG) induction plus long-term maintenance treatment for high-grade superficial bladder cancer. METHODS Between 1994 and 2000, 41 patients who presented to our clinic with superficial urothelial carcinoma of the bladder (T1G3, T1G3 plus carcinoma in situ, or recurrent TaG2-3) were treated by transurethral resection of all visible tumor and an induction cycle of BCG plus a long-term maintenance BCG course consisting of 11 monthly instillations followed by 4 quarterly instillations and then by 6 six-monthly instillations. The median follow-up was 40 months. RESULTS Thirty patients remained tumor free throughout the follow-up period. Ten patients had a recurrence of superficial tumor, 9 patients during the monthly instillation course and 1 patient during the quarterly instillation course. One patient presented with progression. CONCLUSIONS Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment for high-grade superficial bladder cancer. Our maintenance course of BCG seemed to improve the worldwide accepted effectiveness of the BCG induction course without any important side effects.