Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort.

BACKGROUND: Recently a possible link between elevated Chromogranin A (CgA) levels and poorly differentiated prostate cancer has been proposed. The aim of our study was to explore the association of CgA levels and the risk of poorly differentiated prostate cancer (PCa) in men undergoing radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: From 2012 onwards, 335 consecutive men undergoing RRP for PCa at three centers in Italy were enrolled into a prospective database. Body mass index (BMI) was calculated before RRP. Blood samples were collected and tested for total prostate-specific antigen (PSA) levels and chromogranin A (CgA). We evaluated the association between serum levels of CgA and upstaging and upgrading using logistic regression analyses. RESULTS: Median age and preoperative PSA levels were 65 years (interquartile range [IQR]: 60-69) and 7.2 ng/ml (IQR: 5.3-10.4), respectively. Median BMI was 26.1 kg/m2 (IQR: 24-29) with 56 (16%) obese (BMI ≥ 30 kg/m2 ). Median CgA levels were 51 (39/71). Overall, 129/335 (38,5%) presented an upstaging, and 99/335 (30%) presented an upgrading. CgA was not a predictor of upstaging or upgrading on RP. CONCLUSIONS: In our multicenter cohort of patients, CgA is not a predictor of poorly differentiated PCa on radical prostatectomy. According to our experience, CgA should not be considered a reliable marker to predict poorly differentiated or advanced prostate cancer.

Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study.

BACKGROUND: Prostate cancer (PCa) is the most common non-skin cancer in USA and the second leading cause of cancer death in Western Countries. Despite the high mortality associated with PCa, the only established risk factors are age, race and family history. A possible association between metabolic syndrome (MetS) and PCa was firstly described in 2004 and several subsequent studies in biopsy cohorts have shown conflicting results. Aim of our multicentre prospective study was to investigate the association between MetS and PCa in men undergoing radical prostatectomy (RP). METHODS: From January 2012 to June 2015, 349 consecutive men undergoing RP for PCa at three centres in Italy were enrolled into a prospective database. Body Mass Index (BMI) as well as waist circumference was measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Blood pressure was also recorded. We evaluated the association between MetS, defined according to Adult Treatment Panel III, PCa stage (advanced stage defined as pT ≥ 3 or N1) and grade (high grade defined as Gleason Score ≥ 4 + 3) using logistic regression analyses. RESULTS: Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7 ng/ml (IQR: 5-10), respectively. Median BMI was 26.12 kg/m(2) (IQR 24-29) with 56 (16 %) obese (BMI ≥ 30 kg/m(2)) patients and 87 (25 %) patients with MetS. At pathological evaluation, advanced PCa and high-grade disease were present in 126 (36 %) and 145 (41.5 %) patients, respectively. MetS was significantly associated with advanced PCa (45/87, 51 % vs 81/262, 31 %; p = 0.008) and high-grade disease (47/87, 54 % vs 98/262, 37 %; p = 0.001). On multivariable analysis, MetS was an independent predictor of pathological stage ≥ pT3a or N1 (OR: 2.227; CI: 1.273-3.893; p = 0.005) and Gleason score ≥ 4 + 3 (OR: 2.007, CI: 1.175-3.428; p = 0.011). CONCLUSIONS: We firstly demonstrated in a European radical retropubic prostatectomy cohort study that MetS is associated with an increased risk of high-grade and advanced prostate cancer. Further studies with long term follow-up should evaluate the impact of Mets on PCa survival.

Development and external validation of nomograms predicting disease-free and cancer-specific survival after radical cystectomy.

PURPOSE: To develop two nomograms predicting disease-free survival (DFS) and cancer-specific survival (CSS) and to externally validate them in multiple series. METHODS: Prospectively collected data from a single-centre series of 818 consecutive patients who underwent RC and PLND were used to build the nomogram. External validation was performed in 3,173 patients from 7 centres worldwide. Time to recurrence and to cancer-specific death were addressed with univariable and multivariable analyses. Nomograms were built to predict 2-, 5- and 8-year DFS and CSS probabilities. Predictive accuracy was quantified using the concordance index. RESULTS: Age, pathologic T stage, lymph-node density and extent of PLND were independent predictors of DFS and CSS (p < 0.05). Discrimination accuracies for DFS and CSS at 2, 5 and 8 years were 0.81, 0.8, 0.79 and 0.82, 0.81, 0.8, respectively, with a slight overestimation at calibration plots beyond 24 months. In the external series, predictive accuracies for DFS and CSS at 2, 5 and 8 years were 0.83, 0.82, 0.82 and 0.85, 0.85, 0.83 for European centres; 0.73, 0.72, 0.71 and 0.80, 0.74, 0.68 for African series; 0.76, 0.74, 0.71 and 0.79, 0.76, 0.73 for American series. CONCLUSIONS: These nomograms developed from a contemporary series are simple clinical tools and provide optimal oncologic outcome prediction in all external cohorts.

Stage-specific impact of extended versus standard pelvic lymph node dissection in radical cystectomy.

OBJECTIVES: To evaluate the impact of an extended versus a standard pelvic lymph node dissection on disease-free survival and cancer-specific survival of patients with non-metastatic muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy. METHODS: We retrospectively analyzed data of 933 patients collected in two prospectively-maintained institutional databases between 2002 and 2010. Patients who met inclusion criteria (high-grade urothelial carcinoma, have not undergone neoadjuvant treatments, have not undergone salvage cystectomy) were included for analysis. The upper boundary was the iliac bifurcation for standard lymph-node dissection and the aortic bifurcation for the extended lymph node dissection, respectively. Univariable and multivariable Cox regression analyses were carried out to identify independent predictors of disease-free survival and cancer-specific survival and, subsequently, the effect of extended lymph node dissection was determined with a multivariable Cox analysis after stratifying for significant covariates. RESULTS: At multivariable analysis, once adjusted for the effect of the other covariates, extended lymph node dissection was an independent predictor of disease-free survival (hazard ratio 1.95, P < 0.001) and cancer-specific survival (hazard ratio 1.80, P < 0.001). The benefit of an extended pelvic lymph node dissection on disease-free survival and cancer-specific survival was significant across all pT stages (all P < 0.05) except for pT <2 and across all pN stages (pN = 0, P = 0.011 and P = 0.034 for disease-free survival and cancer-specific survival, respectively; pN1 and pN2, all P < 0.001). CONCLUSIONS: The staging accuracy and the survival benefit provided by extended pelvic lymph node dissection suggests the adoption of this template as the standard template for patients with muscle-invasive urothelial carcinoma of the bladder undergoing radical cystectomy.

Patient and Context Factors in the Adoption of Active Surveillance for Low-Risk Prostate Cancer.

Importance: Although active surveillance for patients with low-risk prostate cancer (LRPC) has been recommended for years, its adoption at the population level is often limited. Objective: To make active surveillance available for patients with LRPC using a research framework and to compare patient characteristics and clinical outcomes between those who receive active surveillance vs radical treatments at diagnosis. Design, Setting, and Participants: This population-based, prospective cohort study was designed by a large multidisciplinary group of specialists and patients' representatives. The study was conducted within all 18 urology centers and 7 radiation oncology centers in the Piemonte and Valle d'Aosta Regional Oncology Network in Northwest Italy (approximate population, 4.5 million). Participants included patients with a new diagnosis of LRPC from June 2015 to December 2021. Data were analyzed from January to May 2023. Exposure: At diagnosis, all patients were informed of the available treatment options by the urologist and received an information leaflet describing the benefits and risks of active surveillance compared with active treatments, either radical prostatectomy (RP) or radiation treatment (RT). Patients choosing active surveillance were actively monitored with regular prostate-specific antigen testing, clinical examinations, and a rebiopsy at 12 months. Main Outcomes and Measures: Outcomes of interest were proportion of patients choosing active surveillance or radical treatments, overall survival, and, for patients in active surveillance, treatment-free survival. Comparisons were analyzed with multivariable logistic or Cox models, considering centers as clusters. Results: A total of 852 male patients (median [IQR] age, 70 [64-74] years) were included, and 706 patients (82.9%) chose active surveillance, with an increasing trend over time; 109 patients (12.8%) chose RP, and 37 patients (4.3%) chose RT. Median (IQR) follow-up was 57 (41-76) months. Worse prostate cancer prognostic factors were negatively associated with choosing active surveillance (eg, stage T2a vs T1c: odds ratio [OR], 0.51; 95% CI, 0.28-0.93), while patients who were older (eg, age ≥75 vs <65 years: OR, 4.27; 95% CI, 1.98-9.22), had higher comorbidity (Charlson Comorbidity Index ≥2 vs 0: OR, 1.98; 95% CI, 1.02-3.85), underwent an independent revision of the first prostate biopsy (OR, 2.35; 95% CI, 1.26-4.38) or underwent a multidisciplinary assessment (OR, 2.65; 95% CI, 1.38-5.11) were more likely to choose active surveillance vs active treatment. After adjustment, center at which a patient was treated continued to be an important factor in the choice of treatment (intraclass correlation coefficient, 18.6%). No differences were detected in overall survival between active treatment and active surveillance. Treatment-free survival in the active surveillance cohort was 59.0% (95% CI, 54.8%-62.9%) at 24 months, 54.5% (95% CI, 50.2%-58.6%) at 36 months, and 47.0% (95% CI, 42.2%-51.7%) at 48 months. Conclusions and Relevance: In this population-based cohort study of patients with LRPC, a research framework at system level as well as favorable prognostic factors, a multidisciplinary approach, and an independent review of the first prostate biopsy at patient-level were positively associated with high uptake of active surveillance, a practice largely underused before this study.

Development and external validation of lymph node density cut-off points in prospective series of radical cystectomy and pelvic lymph node dissection.

OBJECTIVE: To identify lymph node density thresholds and their prognostic role in patients who underwent radical cystectomy and pelvic lymph node dissection, and to validate findings in an external series. METHODS: Between May 2001 and September 2009, data from 750 radical cystectomies carried out at "Regina Elena" National Cancer Institute (Rome, Italy) were collected in a prospectively-maintained database. Once patients who had undergone neoadjuvant treatments and those who had undergone salvage radical cystectomy were excluded from the 210 pN+ patients, 156 patients with urothelial carcinoma were selected for analysis. Optimal cut-off points for age, lymph node count and lymph node density were identified by considering these variables as continuous. External validation of findings was carried out by using data of 154 pN+ patients selected from two prospective series. RESULTS: The optimal identified cut-off points were 11% and 30% for lymph node density, nine and 30 nodes for lymph node count, and 73 years for age. Median cancer-specific survival of patients were significantly different in patients with lymph node density <12%, between 12% and 30%, and >30% (71 months, 24 months and 11 months, respectively; P < 0.001). Cancer-specific survival was independently predicted by lymph node density cut-off points (12-30% vs <12%: hazard ratio 1.51, P = 0.047; >30% vs <12%: hazard ratio 2.89, P < 0.001). In the external series, the prognostic effect of lymph node density according to tertiary distribution of risk based on these lymph node density cut-off points was confirmed at Cox multivariable analysis (12-30% vs <12%: hazard ratio 1.5, P = 0.048; >30% vs <12%: hazard ratio 2.5, P = 0.004). CONCLUSIONS: Lymph node density is the strongest predictor of cancer-specific survival. Identified lymph node density thresholds have shown to be independent predictors of cancer-specific survival in the external validation series.

Laparoscopic high-intensity focused ultrasound for renal tumours: a proof of concept study.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence What's known on the subject? and What does the study add? Renal cancer is increasingly diagnosed when tumours are small and asymptomatic, during routine abdominal imaging. Whilst surgery is an effective and potentially curative option, it carries a significant risk of complications. Recent work suggests that thermally ablative therapies (RFA, cryotherapy, HIFU) may be suitable minimally invasive treatment options in selected patients. The success of extracorporeal HIFU has been limited by the abdominal wall and rib-cage limiting energy delivery. For this study, a purpose-built laparoscopic HIFU probe was designed to allow direct application of the transducer to the tumour surface, thus facilitating tumour destruction. Successful and accurate tumour destruction was demonstrated, paving the way for further clinical trials, subject to device modifications. OBJECTIVE: • To test and establish clinical proof of concept for a laparoscopic high-intensity focused ultrasound (HIFU) device that facilitates delivery of ultrasound by direct application of a probe to the tumour surface. PATIENTS AND METHODS: • Twelve patients with renal tumours were treated with laparoscopic HIFU using a newly designed probe inserted via an 18-mm laparoscopic port. • HIFU treatment was targeted at a pre-defined proportion of the tumour and immediate laparoscopic partial or radical nephrectomy was then performed. RESULTS: • No tumour ablation was seen in the first five patients which made modifications in the treatment protocol necessary. After this, definite histological evidence of ablation was seen in the remaining seven patients. • The ablated zones were within the targeted area in all patients and no intra-lesional skipping was seen. • Subcapsular skipping was seen at the probe-tumour interface in two patients with viable tumour cells seen at microscopy. • One patient did not undergo surgical extirpation; subsequent biopsy revealed no viable tumour cells. • There were no intraoperative or postoperative complications directly related to HIFU therapy and patients have reached a mean (range) follow-up of 15 (8-24) months with no evidence of metastatic disease or late complications. CONCLUSIONS: • Tumour ablation with laparoscopic HIFU is feasible. • Homogenous ablation can be achieved with no vital tissue within the targeted zone. • The technique is associated with low morbidity and may have a role in the definitive management of small tumours.

Minimally Invasive Buccal Mucosa Dorsal Graft for Female Distal Urethroplasty.

BACKGROUND: Female urethral stricture (FUS) represents a sporadic condition. There is a lack of data and standardized guidelines on diagnostics and therapeutics. Several surgical techniques have been described for FUS urethroplasty, among which the flap-based or graft-based ones are most reported. Buccal mucosa graft (BMG) represents the gold standard for male urethroplasty, and this can theoretically be applied also to FUS treatment. OBJECTIVE: To describe and present preliminary results of a novel minimally invasive technique for buccal mucosa dorsal graft (mini-dorsal BMG) urethroplasty for the treatment of FUS. DESIGN SETTING AND PARTICIPANTS: This is a retrospective study on buccal mucosa dorsal graft urethroplasty for the treatment of FUS. SURGICAL PROCEDURE: Every patient was placed in lithotomic position. Two stiches were placed at 10 and 2 o'clock positions to facilitate the dorsal median urethrotomy. The margins of the incised dorsal urethra at the 12 o'clock position are then dissected from the periurethral tissue. This dissection results in an elliptical raw area between the edges of the urethra over the periurethral tissue. The harvested BMG was fixed with several quilting sutures, using 5-0 and 4-0 absorbable sutures, to cover the raw area. The margins of the graft were sutured to the edges of the incised urethra. MEASUREMENTS: A chart review was performed. RESULTS AND LIMITATIONS: Thirteen patients underwent the mini-dorsal-BMG technique. The median preoperative uroflow was 5.6 (3-13) ml/s, and the median postoperative value was 23.4 (14-58) ml/s. CONCLUSIONS: The mini-dorsal-BMG technique for the treatment of FUS gives good results with low complication rates. Other series and long-term follow-up are necessary to confirm the reproducibility of this technique. PATIENT SUMMARY: We present the technical aspects and the promising preliminary results of a novel surgical technique for the treatment of female urethral stricture by using the buccal mucosa to correct this invalidating disease.

Diagnostic and prognostic potential of the proteomic profiling of serum-derived extracellular vesicles in prostate cancer.

Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-ß5, Survivin, TGF-ß, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.

Visually directed transrectal high intensity focused ultrasound for the treatment of prostate cancer: a preliminary report on the Italian experience.

PURPOSE: High intensity focused ultrasound is a minimally invasive treatment option for prostate cancer. Data from the literature show promising early oncological outcomes and a favorable side effect profile. This study is a preliminary report of the Italian experience (Perugia and Turin) of patients treated with the Sonablate(R)500 high intensity focused ultrasound device. MATERIALS AND METHODS: Between 2004 and 2007, 163 consecutive men with T1-T3 N0M0 prostate cancer underwent high intensity focused ultrasound with the Sonablate 500. Followup included prostate specific antigen tests at 1 month and then every 3 months after treatment, and a random prostate biopsy at 6 months. Failure was defined according to prostate specific antigen nadir, positive findings on followup biopsy and biochemical failure according to Phoenix criteria. RESULTS: Median patient age was 72 years old, median baseline prostate specific antigen was 7.3 ng/ml, and disease stage was T1 in 44.1%, T2 in 42.5% and T3a in 13.4% of patients. Median followup was 23.8 months. After high intensity focused ultrasound treatment prostate specific antigen decreased to a median nadir of 0.15 ng/ml. Median prostate specific antigen at 3 and 6 months was 0.30 and 0.54 ng/ml, respectively. At 6 months the negative biopsy rate was 66.1%. There was no biochemical evidence of disease in 71.9% overall. On multivariate analysis prostate specific antigen nadir became the only independent predictor of no biochemical evidence of disease and positive biopsy at a cutoff of 0.40 ng/ml. CONCLUSIONS: A favorable outcome of high intensity focused ultrasound is associated with lower baseline prostate specific antigen, lower prostate specific antigen nadir, lower Gleason score and lower tumor stage. As with any novel technology long-term data will be required before this technique gains widespread clinical acceptance.

Transrectal-HIFU as primary minimally-invasive option for localized prostate cancer. Is spinal anaesthesia cost-effective? A single centre experience in over 100 patients.

INTRODUCTION: The management of Prostate cancer (PC), since PSA testing has been introduced in the clinical practice, has been significantly spoiled by a "leading-time bias" effect. As a consequence, this has brought to a dramatic diagnosis anticipation at the 4th-5th decade of life in sexually active and otherwise asymptomatic men. Standard options as radical prostatectomy or EBRT are hampered by a significant negative impact on patient's QoL. More recently several alternative minimally-invasive ablative treatment modalities have been proposed with promising results. Among these, TR-HIFU (Trans-Rectal High Intensity Focused Ultrasound) is playing a growing role in the treatment of localized low-intermediate risk PC, although long-term oncologic outcome are still awaited. In order to achieve an optimal result, a specific TR-HIFU's requirement is given by an unchanging target throughout the whole procedure. Therefore, the ideal anaesthesia should be either minimally-invasive and allow to get a motionless target up to 3-4 hours. A retrospective evaluation of efficacy and safety of a spinal anaesthesia in this patient's setting was done. MATERIAL AND METHODS: 107 patients with localized prostate cancer treated in our institution from October 2004 to December 2007 with TR-HIFU procedure received a subarachnoidal anaesthesia with combined administration of 0.5% normobaric racemic bupivacaine (15 to 17.5 mg) and sufentanil 5 microg. RESULTS: This technique allowed covering the whole TR-HIFU procedure (analgesia and motor blockade up to 4-5 hours). It was well tolerated by patients who only rarely required additional sedative or analgesics. A low anaesthesia-related side effects rate, as arterial hypotension, nausea and vomiting, and no severe side effects of intrathecal opioids, as deep sedation, bradycardia, myosis, bradypnea and oxygen desaturation, occurred. Intraoperative employment of sedatives and postoperative need of analgesics was low. CONCLUSIONS: Using a low-dose intrathecal sufentanil an effective spinal block either on the sensitive and motor pathways was provided. Patients' tolerance to the procedure was good and the side-effect rate low. No adverse reactions to intrathecal sufentanil 5 microg were observed. In our experience TR-HIFU can be performed with neuraxial block in most of the cases and it's associated to a favorable cost-benefit rate.

Correction: Metabolic syndrome increases the risk of upgrading and upstaging in patients with prostate cancer on biopsy: a radical prostatectomy multicenter cohort study.

The original version of this Article contained an error in the spelling of the authors Cosimo De Nunzio, Aldo Brassetti, Giuseppe Simone, Riccardo Lombardo, Riccardo Mastroianni, Devis Collura, Giovanni Muto, Michele Gallucci and Andrew Tubaro, which were incorrectly given as De Nunzio Cosimo, Brassetti Aldo, Simone Giuseppe, Lombardo Riccardo, Mastroianni Riccardo, Collura Devis, Muto Giovanni, Gallucci Michele and Tubaro Andrea. This has now been corrected in both the PDF and HTML versions of the Article.

Modulation of neuropeptide Y and Y1 receptor expression in the amygdala by fluctuations in the brain content of neuroactive steroids during ethanol drinking discontinuation in Y1R/LacZ transgenic mice.

Previous studies have shown that GABAergic neuroactive steroids increase Y1 receptor (Y1R) gene expression in the amygdala of Y1R/LacZ transgenic mice, harbouring the murine Y1R gene promoter linked to a LacZ reporter gene. As ethanol is known to increase GABAergic neuroactive steroids, we investigated the relationship between fluctuations in the brain content of neuroactive steroids induced by chronic voluntary ethanol consumption or ethanol discontinuation and both the level of neuropeptide Y (NPY) immunoreactivity and Y1R gene expression in the amygdala of Y1R/LacZ transgenic mice. Ethanol discontinuation (48 h) after voluntary consumption of consecutive solutions of 3%, 6%, 10% and 20% (v/v) ethanol over 4 weeks produced an anxiety-like behaviour as measured by elevated plus maze. Voluntary ethanol intake increased the cerebrocortical concentration of the progesterone metabolite 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG) that returned to control level 48 h after discontinuation of ethanol intake. Ethanol discontinuation significantly decreased NPY immunoreactivity and concomitantly increased Y1R/LacZ transgene expression in the amygdala, whereas chronic ethanol intake failed to affect these parameters. The 5alpha-reductase inhibitor finasteride prevented both the increase in the cerebrocortical concentration of 3alpha,5alpha-TH PROG apparent after 4 weeks of ethanol intake and the changes in NPY immunoreactivity and transgene expression induced by ethanol discontinuation. Data suggest that 3alpha,5alpha-TH PROG plays an important role in the changes in NPY-Y1R signalling in the amygdala during ethanol discontinuation.

Metabolic syndrome increases the risk of upgrading and upstaging in patients with prostate cancer on biopsy: a radical prostatectomy multicenter cohort study.

BACKROUND: Recently metabolic syndrome has been associated to an increased risk of advanced disease. Aim of our study is to investigate the association of metabolic syndrome (MetS) with the risk of prostate cancer (PCa) upgrading and upstaging after radical prostatectomy (RP). METHODS: From 2012 and 2016, 400 consecutive men underwent RP at three referral centers in Italy and were enrolled into a prospective database. Blood pressure, body mass index and waist circumference were measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Logistic regression analyses were used to assess the association between MetS, defined according to Adult Treatment Panel III, and the risk of upgrading and upstaging), using the new Prognostic Grade Group (PGG) classification system. RESULTS: Overall 148/400 (37%) men were diagnosed with MetS and most of these reported up-grading (54.5%) and up-staging (56.8%). These events were significantly more common in this population and MetS was a risk factor for up-staging and up-grading on multivariable analysis. Patients with MetS presented worst accuracy (72 vs. 84%; p = 0.001) and worst kappa coefficient of agreement (k = 0.439 ± 0.071 vs. k = 0.553 ± 0.071) between needle biopsy and radical prostatectomy specimens when compared to patients without MetS. CONCLUSIONS: MetS represents a significant risk factor for upgrading and upstaging. Accuracy of PGG system on biopsy is poor in patients with MetS, therefore results should be evaluated carefully in this population.

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients.

PURPOSE: To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. MATERIALS AND METHODS: Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. RESULTS: The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p = .001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p = .267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). CONCLUSIONS: The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management.

Adjuvant helical IMRT by tomotherapy for bulky adrenocortical carcinoma operated with positive margins: a case report.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumor in the adult. The main therapy is surgery but in some cases radiotherapy may be needed to control the disease locally. METHODS: A patient with a surgically removed bulky ACC and pathologic finding of a positive margin was treated at our center by adjuvant mitotane and radiotherapy using an intensity-modulated radiation therapy (IMRT)/image-guided radiotherapy (IGRT) technique by tomotherapy. Dose prescriptions were 63 Gy on the surgical bed and 50.4 Gy on the lymphatic drainage in 28 sessions. Patient compliance was good with no evidence of acute or late toxicities. RESULTS: Thirty months after radiotherapy, the patient is alive without evidence of disease checked by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and without any complication. CONCLUSIONS: In patients with adverse prognostic features, the delivery of adequate adjuvant radiotherapy doses with IMRT and daily IGRT is feasible and safe and could result in an improved outcome for patients with ACC.

High-intensity focused ultrasound for the treatment of prostate cancer: A prospective trial with long-term follow-up.

OBJECTIVE: High-intensity focused ultrasound (HIFU) is a minimally invasive treatment for prostate cancer. Data from the literature show promising oncological outcomes with a favourable side-effect profile. The aim of this study was to re-evaluate and bring up to date the follow-up of a previously published, prospective trial on HIFU as the primary treatment for prostate cancer. MATERIALS AND METHODS: Between 2004 and 2007, 163 consecutive men with T1-T3N0M0 prostate cancer underwent HIFU with the Sonablate 500. Follow-up included prostate-specific antigen (PSA) tests every 3 months after treatment and a random prostate biopsy at 6 months. Failure was defined according to positive findings at the 6 month biopsy and biochemical failure was defined according to the Phoenix criteria. Biochemical-free survival, metastasis-free survival and cancer-specific survival were calculated by Kaplan-Meier curves. RESULTS: Median follow-up was 72.0 months. Of the 160 evaluable patients, 104 (65%) were biochemically disease free; in low- to intermediate-risk disease, on Kaplan-Meier analysis the 8 year biochemical-non-evidence of disease (bNED), metastasis-free survival and cancer-specific survival rates were 69.6%, 81.3%, 100% and 40.5%, 60.6%, 100%, respectively. A PSA nadir below 0.40 ng/ml and risk stratification have an independent predictive value for bNED and metastasis-free survival. CONCLUSIONS: A long-term favourable outcome of HIFU is associated with careful patient selection, with low- to intermediate-risk disease being the ideal case. A low postoperative PSA nadir is a predictor of long-term bNED.

Seminal-sparing cystectomy: technical evolution and results over a 20-year period.

OBJECTIVE: To demonstrate the oncologic and functional results of seminal-sparing cystectomy (SSC) in patients with bladder cancer (BC) and to describe the evolution of our surgical technique over a 20-year period. METHODS: From 1990 to 2009 we performed SSC in 88 patients with non-muscle-invasive BC and in 10 patients with muscle-invasive BC away from the bladder neck. Sixty-one of the 98 patients (1990-2002) underwent cystoadenomectomy with ileocapsuloplasty (ICP), consisting of the anastomosis between the Camey II ileal reservoir and the upper edge of the prostatic capsule. This technique was affected by a relevant percentage of anastomotic stricture (11%). From 2003 to 2009, we performed the endocapsular ileourethral anastomosis (EIUA) in 30 patients, on the basis of the direct anastomosis between the ileal reservoir and the urethral stump inside the prostatic apex. Seven patients were lost to follow-up. RESULTS: After a mean follow-up of 102 months, 81 patients (89%) were alive, and 10 patients (11%) had died (8 of disease progression). Early and late complication rates were 25% and 24%, respectively. Complete daytime continence was obtained in 87 patients (95.6%), and nighttime continence was achieved in 34 patients (37%). In the ICP group, stricture of the prostatic fossa affected 7 patients (11%), whereas no neobladder-urethral anastomosis stricture was noticed in the EIUA group. Normal erectile function was preserved in 87 patients (95.6%). CONCLUSION: SSC offers good oncologic and functional results in carefully selected patients. EIUA represents an evolution from ICP because EIUA reduces the risk of stenosis.

Thulium:yttrium-aluminum-garnet laser for en bloc resection of bladder cancer: clinical and histopathologic advantages.

OBJECTIVE: To determine whether thulium:yttrium-aluminum-garnet laser resection of bladder tumor (TmLRBT) may offer advantages over classic resection. MATERIALS AND METHODS: From April 2011 to September 2012, 55 consecutive patients newly diagnosed with clinical stage ≤T2 bladder cancer were enrolled in a prospective study on TmLRBT. Neoplasm was removed en bloc in all cases. When the tumor size was >3 cm, it was necessary to incise longitudinally and/or across the lesion and the bladder wall at its the base into 2 or more parts. All cases of non-muscle-invasive bladder cancer underwent second look in 30-90 days. RESULTS: Pathology reported urothelial carcinoma with Ta low grade in 31 patients (56.4%), T1 high grade in 18 (32.7%), and T2 high grade in 6 (10.9%). Histopathologic evaluation showed that the bladder detrusor was provided in all cases. Hemostasis was excellent, and no postoperative hematuria was reported. In a case of T1 G3, endoscopic re-evaluation showed a focal infiltration of the bladder detrusor, so the patient underwent radical cystectomy. To date, with a mean follow-up of 16 months (range, 8-25), the recurrence rate in patients with superficial disease is 14.5%. All recurrences were outside the site of first resection, and there was no progression in tumor grade. CONCLUSION: TmLRBT is a simple method that seems to overcome the "incise and scatter" problem associated with traditional transurethral resection of bladder tumor. Our initial data on staging accuracy and reduction of the local recurrence rate are encouraging.

Huge anterior sacral meningocele simulating bladder retention.

Anterior sacral meningocele (ASM) is a rare congenital disorder involving herniation of the dural sac through a defect in the anterior surface of the sacrum. We report the case of a young patient with an enormous ASM that simulated bladder retention in terms of symptoms as well as on physical examination and at ultrasonography. After introducing a catheter that excluded urinary retention, computed tomography (CT) scan and magnetic resonance imaging (MRI) showed the ASM. The patient underwent surgical repair of the ASM through a sacral laminectomy and recovered normal lower urinary tract function.