Francesco Rocco

Restoration of Posterior Aspect of Rhabdosphincter Shortens Continence Time After Radical Retropubic Prostatectomy

PURPOSEnProlonged postoperative incontinence is a major drawback of RRP. Age, scars in the rhabdosphincter, nonnerve sparing surgery and postoperative sphincter insufficiency can cause temporary or definitive urinary incontinence. We believe that sphincter deficiency is the main cause of early incontinence. Urinary leakage results from the shortening of anatomical and functional sphincter length due to caudal retraction of the urethral sphincteric complex and disruption of the median posterior fibrous raphe. We describe a modification of the Walsh RRP that overcomes caudal retraction, reconstructs the posterior fibrous raphe and decreases time to continence. The primary study end point was early continence rate assessment. Long-term continence (1 year) and erectile function assessment were secondary end points.nnnMATERIALS AND METHODSnTo avoid caudal retraction of the urethrosphincteric complex, before completing the vesicourethral anastomosis the posterior semicircumference of the sphincter is joined to the residuum of Denonvilliers fascia and fixed to the posterior bladder wall 1 to 2 cm cranial and dorsal to the new bladder neck. Vesicourethral anastomosis is subsequently performed with care taken not to involve the neurovascular bundles. A total of 161 patients with clinically confined disease underwent modified RRP (group 1). They were compared with a historical series of 50 patients who underwent standard RRP (group 2). Early continence was defined as no pad use but patients using 1 diaper were also considered continent. Continence, assessed prospectively as the number of pads daily, was evaluated 3, 30 and 90 days, and 1 year after catheter removal. The continence state was assessed by a multivariate logistic model. Erectile function was evaluated using the International Index of Erectile Function questionnaire preoperatively and after 18 months in patients younger than 65 years who underwent nerve sparing surgery.nnnRESULTSnIn group 1, 116 (72%), 127 (78.8%) and 139 patients (86.3%) were continent 3, 30 and 90 days after catheter removal compared with 7 (14%), 15 (30%) and 23 (46%), respectively, in group 2. One-year continence rates were 96% and 90%, respectively. Erectile function was similar in groups 1 and 2 (46% and 42%, respectively). Multivariate analysis showed that continence was significantly influenced by operation type, stage and patient age.nnnCONCLUSIONSnCareful reconstruction of the posterior aspect of the rhabdosphincter markedly shortens time to continence.

Simple Enucleation is Equivalent to Traditional Partial Nephrectomy for Renal Cell Carcinoma: Results of a Nonrandomized, Retrospective, Comparative Study

PURPOSEnThe excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation.nnnMATERIALS AND METHODSnWe retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival.nnnRESULTSnMedian followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates.nnnCONCLUSIONSnTo our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile.

BackgroundClear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.ResultsWe performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.ConclusionBy combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.

Human urine biomarkers of renal cell carcinoma evaluated by ClinProt

Renal cell carcinoma (RCC) is one of the major causes of cancer death and is radio‐ and chemoresistant. Urine of 29 healthy subjects and 39 clear cell RCC patients were analyzed using the ClinProt technique to search for possible biomarkers for early RCC diagnosis. A cluster of three signals (marker A= at m/z 1827u2005±u20058u2005Da, marker B = 1914u2005±u20058u2005Da and marker C = 1968u2005±u20058u2005Da) was able to discriminate patients from controls. A receiver operating characteristic curve analysis showed values of area under the curve (AUC) higher than 0.9 for marker A and B, corresponding to a sensitivity of 85–90% and a specificity of 90%, while marker C gave a lower AUC (0.84) corresponding to sensitivity of 70% and specificity of 100%. The combination of three markers lead to an improvement in diagnostic efficacy, with specificity and sensitivity of 100% and 95%, respectively, in the training test and of 100% and of 85% in the test experiment. The efficacy of this cluster of signals to distinguish RCC patients grouped by tumor stage showed a sensibility of 100% for patients at the primary tumor 1 stage. One of the signals present in the cluster was identified as a fragment of Tamm‐Horsfall protein.

Simple enucleation versus standard partial nephrectomy for clinical T1 renal masses: Perioperative outcomes based on a matched-pair comparison of 396 patients (RECORd project)

OBJECTIVESnTo compare simple enucleation (SE) and standard partial nephrectomy (SPN) in terms of surgical results in a multicenter dataset (RECORd Project).nnnMATERIALS AND METHODSnpatients treated with nephron sparing surgery (NSS) for clinical T1 renal tumors between January 2009 and January 2011 were evaluated. Overall, 198 patients who underwent SE were retrospectively matched to 198 patients who underwent SPN. The SPN and SE groups were compared regarding intraoperative, early post-operative and pathologic outcome variables. Multivariable analysis was applied to analyze predictors of positive surgical margin (PSM) status.nnnRESULTSnSE was associated with similar WIT (18 vs 17.8 min), lower intraoperative blood loss (177 vs 221 cc, p = 0.02) and shorter operative time (121 vs 147 min; p < 0.0001). Surgical approach (laparoscopic vs. open), tumor size and type of indication (elective/relative vs absolute) were associated with WIT >20 min. The incidence of PSM was significantly lower in patients treated with SE (1.4% vs 6.9%; p = 0.02). At multivariable analysis, PSM was related to the surgical technique, with a 4.7-fold increased risk of PSM for SPN compared to SE. The incidence of overall, medical and surgical complications was similar between SE and SPN.nnnCONCLUSIONSnType of NSS technique (SE vs SPN) adopted has a negligible impact on WIT and postoperative morbidity but SE seems protective against PSM occurrence.

Anatomical reconstruction of the rhabdosphincter after radical prostatectomy

The widespread use of PSA has led to an increasing incidence of prostate cancer with a consistent downward stage migration [1], making a surgical approach with curative intents suitable in most cases. Retropubic radical prostatectomy is the reference standard for clinically localized prostate cancer [2] and the surgical technique has been refined over the years, in particular after the anatomical and physiopathological studies by Walsh and Donker [3]. Nevertheless, despite consistent results in terms of oncological outcomes [4], the procedure still has significant drawbacks, among which the most significant are erectile dysfunction and urinary incontinence. According to the European Association of Urology guidelines [5], urinary incontinence persists after 1 year in only 7.7% of patients; however, although most patients eventually recover continence, the period of incontinence is poorly tolerated BJUI

Differential expression of AQP1 in microdomain-enriched membranes of Renal Cell Carcinoma

Human aquaporin‐1 (AQP1) is the most studied member of the aquaporin family, acting as molecular water channel. It is also considered a differentiation marker for proximal renal tubular cells, from which clear cells renal cell carcinoma (RCC) originates, playing an important role in urine formation. We therefore studied AQP1 expression at the proteomic level in RCC and normal tissues, mainly focusing on microdomain‐enriched membranes in which AQP1 is highly concentrated. Subcellular fractions were prepared through differential centrifugation, and microdomain‐enriched fractions were purified from a plasma membrane‐enriched fraction by 1% Triton X‐100 treatment followed by ultracentrifugation in sucrose gradient. After SDS‐PAGE and Western blot analyses with antibodies against AQP1, lower expression levels of AQP1 isoforms were observed in each subcellular fraction of RCC compared to fractions from normal kidney tissues. The presence of AQP1 in the immunoreactive bands was verified by MALDI‐TOF‐MS and LC‐ESI‐MS/MS analysis. Glycosylation of AQP1 was also investigated using N‐glycosidase F, confirming the presence of a N‐glycosylated isoform of AQP1 in the 35–45‐kDa region. These results highlight an under‐expression of AQP1 protein and its glycosylated isoforms in homogenate and subcellular fraction obtained from RCC tissue compared to adjacent normal cortex.

Male Urethral Strictures: A National Survey Among Urologists in Italy

OBJECTIVEnTo determine national practice patterns in the management of male urethral strictures among Italian urologists.nnnMETHODSnWe conducted a survey using a nonvalidated questionnaire mailed to 700 randomly selected Italian urologists. Data were registered into a database and extensively evaluated. Analysis was performed using SAS statistical software (version 9.2). Statistical significance was defined as P ≤.05.nnnRESULTSnA total of 523 (74.7%) urologists completed the questionnaire. Internal urethrotomy and dilatation were the most frequently used procedures (practiced by 81.8% and 62.5% of responders, respectively), even if most urologists (71.5%) considered internal urethrotomy appropriate only for strictures no longer than 1.5 cm; 12% of urologists declared to use stents. Overall, minimally invasive techniques were performed more frequently that any open urethroplasty (P = .012). Particularly, 60.8% of urologists did not perform urethroplasty surgery, 30.8% performed 1-5 urethroplasties yearly, and only 8.4% performed >5 urethroplasty surgeries yearly. The most common urethroplasty surgery was one-stage graft technique, particularly using oral mucosa and ventrally placed. Diagnostic workup and outcome assessment varied greatly.nnnCONCLUSIONnIn Italy, minimally invasive procedures are the most commonly used treatment for urethral stricture disease. Only a minimal part of urologists perform urethroplasty surgery and only few cases per year. The most preferred techniques are not traditional anastomotic procedures but graft urethroplasties using oral mucosa; the graft is preferably ventrally placed rather than dorsally. There is no uniformity in the methods used to evaluate urethral stricture before and after treatment.

Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study

OBJECTIVEnTo analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines.nnnMATERIALS AND METHODSnThe CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded.nnnRESULTSnThe final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index u2009>u20092 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (Pu2009=u2009.96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; Pu2009<u2009.01) and osteoporosis (odds ratio: 1.75; Pu2009=u2009.04).nnnCONCLUSIONnAbout one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription.

Primary large cell neuroendocrine carcinoma of the renal pelvis: a case report.

We report a case of primary large cell neuroendocrine carcinoma of the renal pelvis, diagnosed in a 79-year-old man. The abdominal computed tomography showed a solid, vegetant lesion in the left renal pelvis, conditioning marked hydronephrosis. The patient underwent radical nephroureterectomy. The histological examination showed a large cell neuroendocrine carcinoma associated with a high-grade urothelial carcinoma, with local invasion (pT3). Large cell renal neuroendocrine carcinomas are rare tumors with an aggressive course and a bad prognosis. At present, only five cases were reported in literature.