Urinary microbiota is associated to clinicopathological features in benign prostatic hyperplasia.

BACKGROUND: The urinary microbiota of patients with benign prostatic hyperplasia (BPH) has been associated with lower urinary tract symptoms (LUTS), however, little is known about urinary microbiota correlations with clinicopathological parameters associated with BPH. Here, we investigate associations between the urinary microbiota and clinical parameters of patients with BPH undergoing surgery. METHODS: Forty-one patients with BPH undergoing surgery were recruited from two medical centers. Catheterized urine specimens were collected and the microbiota was characterized by 16S rRNA gene sequencing. Patients were segregated into two groups according to each clinical parameter and differences in urinary microbiota diversity and composition were evaluated. RESULTS: Higher prostate weight and prostate-specific antigen (PSA) levels were associated with higher alpha diversity in the urinary microbiota of BPH patients. At the specific microbe level, we found that the greater the prostatic weight, the lower the relative abundance of Streptococcus, while the greater the PSA levels, the higher the abundance of Lactobacillus. Treatment with 5-α-reductase inhibitor was associated with overall urinary microbiota composition, in part due to a higher abundance of Corynebacterium and Anaerococcus in this group. CONCLUSIONS: We demonstrated that the urinary microbiota of BPH patients is associated with clinicopathological features, paving the way for larger studies in which causality between urinary microbiota and BPH can be appropriately explored.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.

Laparoscopic Ureterocalicostomy Technique

ABSTRACT Purpose: Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the established principles of open surgery. In 2004, Gill et al. had two patients with UPJO treated with laparoscopic ureterocalicostomy, with success (3). In 2014, Arap et. al. presented a case series with good results in adults and children in our service (4). There are factors that prepare the surgeon for an ureterocalicostomy, such as the renal cortex thickness, although the decision is mainly taken during the procedure (5). Material and Methods: A 24 years-old female patient with right lumbar pain was referred to our institution. She already had a right open pyeloplasty two years ago. The CT scan presented a right hydronephrotic kidney, DMSA scan with 30% of relative function and a DTPA scan with an obstructive pattern. Results: A laparoscopic ureterocalicostomy was performed due to the intra-operative findings (inferior kidney pole thickness and challenging access to the uretero-pelvic junction). The overall time was 130 minutes with no complications. The patient was discharged in two days and the double J was withdrawn in four weeks. The CT scan within one year demonstrates a reduction of the hydronephrosis. She had no more lumbar pain. Conclusion: In complex cases, the laparoscopic ureterocalicostomy proves to be a safe and efficient procedure, with a free tension-free anastomosis and the advantages of the laparoscopic access.

Preclinical optimization of a diode laser-based clamp-free partial nephrectomy in a large animal model.

Kidney cancer is a common urologic malignancy with either laparoscopic (LPN) or robotic partial nephrectomy as therapeutic options of choice for localized tumors. However, renal resection and suturing are challenging steps of the procedure that can lead to complications such as prolonged warm ischemia, bleeding, and urinary fistulas. LPN with a diode laser is an efficient technique due to its cutting and/or coagulation attributes. Surprisingly, key laser features such as wavelength and power remain undefined. Using a large porcine model, we evaluated the laser range of wavelength and power in a clamp-free LPN and compared it to the established gold-standard LPN technique (i.e., cold-cutting and suturing). By analyzing surgery duration, bleeding, presence of urine leak, tissue damage related to the resected renal fragment and the remaining organ, hemoglobin levels, and renal function, we show that an optimized experimental diode laser clamp-free LPN (wavelength, 980 nm; power, 15 W) had shorter surgery time with less bleeding, and better postoperative renal function recovery when compared to the well-established technique. Together, our data indicate that partial nephrectomy with a diode laser clamp-free LPN technique is an improved alternative to the gold-standard technique. Therefore, translational clinical trials towards human patient applications are readily feasible.

Laparoscopic Ureterocalicostomy Technique.

PURPOSE: Ureterocalicostomy is a technique that was first described by Neuwirt in 1948 (1) The laparoscopic access was initiated in 2003 by Cherullo et al. (2), following the established principles of open surgery. In 2004, Gill et al. had two patients with UPJO treated with laparoscopic ureterocalicostomy, with success (3). In 2014, Arap et. al. presented a case series with good results in adults and children in our service (4). There are factors that prepare the surgeon for an ureterocalicostomy, such as the renal cortex thickness, although the decision is mainly taken during the procedure (5). MATERIAL AND METHODS: A 24 years-old female patient with right lumbar pain was referred to our institution. She already had a right open pyeloplasty two years ago. The CT scan presented a right hydronephrotic kidney, DMSA scan with 30% of relative function and a DTPA scan with an obstructive pattern. RESULTS: A laparoscopic ureterocalicostomy was performed due to the intra-operative findings (inferior kidney pole thickness and challenging access to the uretero-pelvic junction). The overall time was 130 minutes with no complications. The patient was discharged in two days and the double J was withdrawn in four weeks. The CT scan within one year demonstrates a reduction of the hydronephrosis. She had no more lumbar pain. CONCLUSION: In complex cases, the laparoscopic ureterocalicostomy proves to be a safe and efficient procedure, with a free tension-free anastomosis and the advantages of the laparoscopic access.

Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

Background: We have previously shown that the long non-coding (lnc)RNA prostate cancer associated 3 (PCA3; formerly prostate cancer antigen 3) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene PRUNE2 (a homolog of the Drosophila prune gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the PCA3/PRUNE2 regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression. Methods: The reciprocal PCA3 and PRUNE2 gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497). We compared the tumor gene expression of PCA3 and PRUNE2 to their corresponding expression in the normal prostate. We also serially examined clinical/pathological variables including time to disease recurrence. Results: We consistently observed increased expression of PCA3 and decreased expression of PRUNE2 in prostate cancer compared with the adjacent normal prostate across all tumor grades and stages. However, there was no association between the relative gene expression levels of PCA3 or PRUNE2 and time to disease recurrence, independent of tumor grades and stages. Conclusions: We concluded that upregulation of the lncRNA PCA3 and targeted downregulation of the protein-coding PRUNE2 gene in prostate cancer could be early (rather than late) molecular events in the progression of human prostate tumorigenesis but are not associated with biochemical recurrence. Further studies of PCA3/PRUNE2 dysregulation are warranted. Funding: We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological Development (CNPq), Brazil, and the Associação Beneficente Alzira Denise Hertzog Silva (ABADHS), Brazil. This work has been funded in part by the NCI Cancer Center Support Grants (CCSG; P30) to the University of New Mexico Comprehensive Cancer Center (CA118100) and the Rutgers Cancer Institute of New Jersey (CA072720).

Pyeloplasty in Adults With Ureteropelvic Junction Obstruction in Poorly Functioning Kidneys: A Systematic Review.

OBJECTIVES: To systematically summarize the available evidence concerning the impact of pyeloplasty on symptoms and differential renal function (DRF) in adults with unilateral UPJO in poorly functioning kidneys (PFK), and to identify potential predictors of kidney function recovery that could help clinicians select candidates for pyeloplasty. METHODS: A literature search (MEDLINE, Embase, Google Scholar, Scopus, ClinicalTrials.gov, and the WHO Clinical Trials Registry) and systematic review were performed up to September 2020 according to the PRISMA guidelines. PFK were defined as a baseline DRF ≤30% on renal scintigraphy. The primary endpoints were symptom relief and postoperative scintigraphic DRF. Predictors of kidney function recovery were evaluated and compared among studies. RESULTS: Nine studies comprising 731 patients met the inclusion criteria and were included for evidence synthesis. A DRF increase >5% occurred in 13.3%-53.8% of 160 patients with a pre- and postoperative renal scan. Symptoms improved in 73.3%-93.3% of 141 adults after pyeloplasty. Neither patient's age, baseline DFR, comorbidities, degree of hydronephrosis, kidney parenchymal thickness, nor kidney biopsy findings consistently predicted a significant DRF increase among 375 patients undergoing pyeloplasty. CONCLUSION: Based on a low level of evidence, pyeloplasty may relieve symptoms and stabilize kidney function in adults with UPJO in PFK. A significant number of patients showed a DRF increase >5%, yet no consistent predictor of kidney function recovery was identified. Until more evidence becomes available, pyeloplasty could be considered for selected cases after accounting for the risks of a failure requiring a future nephrectomy.

Short-term outcomes of pyeloplasty vs. nephrectomy in adult patients with ureteropelvic junction obstruction and differential renal function ≤15.

OBJECTIVES: To compare symptom resolution and short-term renal function after pyeloplasty or nephrectomy in adults with ureteropelvic junction obstruction (UPJO) in poorly functioning renal units (PFRU). METHODS: Retrospective analysis of adult patients with UPJO and differential renal function (DRF) ≤ 15% who underwent laparoscopic pyeloplasty or nephrectomy. Primary endpoints included symptom resolution and estimated glomerular filtration rate (eGFR) at 12 months. Surgical complications were compared between groups. A secondary analysis was performed comparing baseline and postoperative DRF to evaluate the PFRU recovery potential after pyeloplasty. RESULTS: Sixty-three patients were included; 19 underwent pyeloplasty and 44 underwent nephrectomy. The mean age of the cohort was 39.5 ± 13.8 years. Nephrectomy was associated with significantly higher intra-operative blood loss (p = 0.02). Operative time and length of hospital stay were not significantly different between groups. There were three complications in the nephrectomy group, and none in the pyeloplasty group (p = 0.34). Symptom resolution rates were equivalent between groups (73% vs. 76%; p = 0.78). The eGFR variation was not statistically different after pyeloplasty or nephrectomy (+6.2 vs. +0.1 mL/min/1.73m2, respectively; p = 0.18). Patients undergoing pyeloplasty had no significant change in the mean DRF (baseline 9.5 vs. 10%; p = 0.99). CONCLUSION: Pyeloplasty can be considered for selected patients with UPJO in PFRU as an organ-sparing alternative to nephrectomy. Although there was no significant gain in mean DRF, pyeloplasty prevented further functional loss and relieved symptoms in most cases in the short-term with at least the same complication rates of nephrectomy.

Percutaneous thermoablation of small renal masses (T1a) in surgical candidate patients: oncologic outcomes.

OBJECTIVE: To evaluate the local tumour progression-free survival (LTPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) of healthy surgical candidates who underwent percutaneous thermoablation (TA) as a first-line therapy for small renal masses (T1a). METHODS: The institutional review board approved this bi-institutional retrospective study of 85 consecutive surgical candidates with 97 biopsy-proven malignant renal masses (T1a) treated with percutaneous TA from 2008 to 2016. The LTPFS, MFS, CSS and OS rates were calculated using the Kaplan-Meier method. Descriptive analysis was also performed. RESULTS: The median tumour size was 2.3 cm (range, 0.7-3.9 cm). The minimal and mean follow-up periods were 24 and 56 months, respectively. Local recurrence was detected in four patients (4.7%) at 8.5, 13.8, 58.0 and 64.0 months of follow-up and retreated successfully with percutaneous TA. No patient developed metastatic renal cell carcinoma, and none died due to renal oncologic complications. One patient died of heart attack. The 5-year LTPFS, OS, MFS and CSS rates were 93.0%, 98.4%, 100% and 100%, respectively. Only two patients (2.3%) had major complications (Clavien-Dindo grade > II), including ureteropelvic junction stenosis and urinary obstruction due to ureteral blood clots. CONCLUSIONS: Our study demonstrates that percutaneous TA is a feasible and effective first-line therapy for healthy surgical candidates with small renal masses (T1a). The 5-year LTPFS, OS, CSS and MFS rates were 93.0%, 98.4%, 100% and 100%, respectively, with a major complication rate of only 2.3%. KEY POINTS: • Image-guided percutaneous thermoablation of small renal malignancies was effective in 95.3% of the healthy surgical candidates. • Major complications were detected in 2.3% of the patients. • The local tumour progression-free survival rate was 97.6% and 93.0% at 3 and 5 years, respectively.

Laparoscopic pyeloplasty as an alternative to nephrectomy in adults with poorly functioning kidneys due to ureteropelvic junction obstruction.

OBJECTIVES: To evaluate outcomes of laparoscopic pyeloplasty (LP) in adults with poorly functioning kidney due to ureteropelvic junction obstruction (UPJO). METHODS: A retrospective comparative analysis was performed between adult patients who underwent LP due to UPJO with differential renal function (DRF) ≤ 15% and DRF > 15%. LP success rate and complications were assessed. LP success was defined as symptoms improvement and DRF improvement or stabilization. DRF and estimated glomerular filtration rate (eGFR) were analyzed before and 12 months after surgery to evaluate renal function recovery. DRF was estimated using Tc-99 m DMSA renal scintigraphy. RESULTS: Among 121 LP performed in the study period at our institution, 15 and 42 were included in the DRF ≤ 15% and DRF > 15% groups, respectively. At a median follow-up of 17.8 months, all patients with DRF ≤ 15% reported symptoms improvement. LP success rate was 86.7% and 90.5% (p = 0.65) for patients with DRF ≤ 15% and DRF > 15%, respectively. There were no complications in the DRF ≤ 15% group, while there were three complications recorded in the DRF > 15% group (Clavien 2 and 3b). In the DRF ≤ 15% group, mean pre-operative and post-operative DRF was 9.5% ± 3.6 and 10.5% ± 7.8 (p = 0.49), respectively. Median pre-operative and post-operative eGFR was 68.5 ml/min and 79.8 ml/min (p = 0.93), respectively. Two patients had DRF improvement after LP. CONCLUSIONS: LP in adult patients with UPJO and poor function kidneys is an effective and safe procedure. DRF recovery is seen in a minority of the patients; however, LP is an alternative to nephrectomy.

Postoperative Renal Function in Patients Undergoing Unilateral Nephrectomy: Development of a Prediction Model Using Preoperative Risk Factors and 51Cr-EDTA Clearance.

Objectives: To analyze the preoperative variables associated to the postoperative glomerular filtration rate (GFR) outcomes after nephrectomy for benign and malignant conditions, measured by the reference isotopic technique 51Cr-ethylene diamine tetra-acetic (51Cr-EDTA) and to create a model to predict the short-term postoperative GFR. Secondary aim was to evaluate which of the common equations for GFR estimation (Cockcroft-Gault, Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) has the best correlation with the 51Cr-EDTA. Methods: Patients undergoing unilateral nephrectomy from 2014 to 2018 were selected. Pre- and postoperative variables were prospectively collected. Univariate and multivariate analyses were done to identify independent risk factors associated with renal function outcomes and to create a model to predict the postoperative GFR. Correlation analyses were performed to evaluate the performance of various serum creatinine-based equations for GFR estimation compared with 51Cr-EDTA. Results: In total, 107 patients were evaluated. After univariate and multivariate analyses, older age (p = 0.008), higher split function of the operated kidney on dimercaptosuccinic acid (DMSA) scintigraphy (p < 0.001), and lower preoperative 51Cr-EDTA (p < 0.001) were independent risk factors for higher GFR decline. Correlation analyses showed that GFR estimated by CKD-EPI equation had the best concordance to GFR measured by 51Cr-EDTA. Conclusions: Based on our findings age, DMSA and lower preoperative 51Cr-EDTA are predictors of postoperative renal function after unilateral nephrectomy. For the assessment of estimated GFR, CKD-EPI equation appears to have the best concordance with 51Cr-EDTA.

Factors affecting urinary continence and sexual potency recovery after robotic-assisted radical prostatectomy

ABSTRACT Introduction Robot-assisted radical prostatectomy (RARP) is the most recent surgical technique for localized prostate cancer. The Da Vinci (Intuitive Surgical, Sunnyvale, CA) system was first introduced in Brazil in 2008, with a fast growing number of surgeries performed each year. Objective Our primary endpoint is to analyze possible predictors of functional outcomes, related to patient and tumor features. As secondary endpoint, describe functional outcomes (urinary continence and sexual potency) from RARP performed in the Sírio-Libanês Hospital (SLH), a private institution, in São Paulo, from April 2008 to December 2015. Materials and Method Data from 104 consecutive patients operated by two surgeons from the SLH (MA and SA) between 2008 and 2015, with a minimum 12 months follow-up, were collected. Patient features (age, body mass index - BMI, PSA, date of surgery and sexual function), tumor features (tumor stage, Gleason and surgical margins) and follow-up data (time to reach urinary continence and sexual potency) were the variables collected at 1, 3, 6 and 12 month and every 6 months thereafter. Continence was defined as the use of no pad on medical interview and sexual potency defined as the capability for vaginal penetration with or without fosphodiesterase type 5 inhibitors. Results Mean age was 60 years old and mean BMI was 28.45 kg/m2. BMI >30kg/m2 (p<0.001) and age (p=0.011) were significant predictors for worse sexual potency after surgery. After 1, 3, 6 and 12 months, 20.7%, 45.7%, 60.9% and 71.8% from patients were potent, respectively. The urinary continence was reached in 36.5%, 80.3%, 88.6% and 92.8% after 1, 3, 6 and 12 months, respectively. Until the end of the study, only one patient was incontinent and 20.7% were impotent. Conclusion Age was a predictor of urinary and erectile function recovery in 12 months. BMI was significant factor for potency recovery. We obtained in a private hospital good functional results after 12 months of follow-up.

Learning robotic pyeloplasty without simulators: an assessment of the learning curve in the early robotic era.

OBJECTIVE: To analyze our experience and learning curve for robotic pyeloplasty during this robotic procedure. METHODS: Ninety-nine patients underwent 100 consecutive procedures. Cases were divided into 4 groups of 25 consecutive procedures to analyze the learning curve. RESULTS: The median anastomosis times were 50.0, 36.8, 34.2 and 29.0 minutes (p=0.137) in the sequential groups, respectively. The median operative times were 144.6, 119.2, 114.5 and 94.6 minutes, with a significant difference between groups 1 and 2 (p=0.015), 1 and 3 (p=0.002), 1 and 4 (p<0.001) and 2 and 4 (p=0.022). The mean hospital stay was 7.08, 4.76, 4.88 and 4.20 days, with a difference between groups 1 and 2 (p<0.001), 1 and 3 (p<0.001) and 1 and 4 (p<0.001). Clinical and radiological improvements were observed in 98.9% of patients. One patient presented with recurrent obstruction. CONCLUSIONS: Our results demonstrate a high success rate with low complication rates. A significant decrease in hospital stay and surgical time was evident after 25 cases.

Factors affecting urinary continence and sexual potency recovery after robotic-assisted radical prostatectomy.

INTRODUCTION: Robot-assisted radical prostatectomy (RARP) is the most recent surgical technique for localized prostate cancer. The Da Vinci (Intuitive Surgical, Sunnyvale, CA) system was first introduced in Brazil in 2008, with a fast growing number of surgeries performed each year. OBJECTIVE: Our primary endpoint is to analyze possible predictors of functional outcomes, related to patient and tumor features. As secondary endpoint, describe functional outcomes (urinary continence and sexual potency) from RARP performed in the Sírio-Libanês Hospital (SLH), a private institution, in São Paulo, from April 2008 to December 2015. MATERIALS AND METHOD: Data from 104 consecutive patients operated by two surgeons from the SLH (MA and SA) between 2008 and 2015, with a minimum 12 months follow-up, were collected. Patient features (age, body mass index - BMI, PSA, date of surgery and sexual function), tumor features (tumor stage, Gleason and surgical margins) and followup data (time to reach urinary continence and sexual potency) were the variables collected at 1, 3, 6 and 12 month and every 6 months thereafter. Continence was defined as the use of no pad on medical interview and sexual potency defined as the capability for vaginal penetration with or without fosphodiesterase type 5 inhibitors. RESULTS: Mean age was 60 years old and mean BMI was 28.45 kg/m2. BMI >30kg/m2 (p<0.001) and age (p=0.011) were significant predictors for worse sexual potency after surgery. After 1, 3, 6 and 12 months, 20.7%, 45.7%, 60.9% and 71.8% from patients were potent, respectively. The urinary continence was reached in 36.5%, 80.3%, 88.6% and 92.8% after 1, 3, 6 and 12 months, respectively. Until the end of the study, only one patient was incontinent and 20.7% were impotent. CONCLUSION: Age was a predictor of urinary and erectile function recovery in 12 months. BMI was significant factor for potency recovery. We obtained in a private hospital good functional results after 12 months of follow-up.

Learning robotic pyeloplasty without simulators: an assessment of the learning curve in the early robotic era

OBJECTIVE: To analyze our experience and learning curve for robotic pyeloplasty during this robotic procedure. METHODS: Ninety-nine patients underwent 100 consecutive procedures. Cases were divided into 4 groups of 25 consecutive procedures to analyze the learning curve. RESULTS: The median anastomosis times were 50.0, 36.8, 34.2 and 29.0 minutes (p=0.137) in the sequential groups, respectively. The median operative times were 144.6, 119.2, 114.5 and 94.6 minutes, with a significant difference between groups 1 and 2 (p=0.015), 1 and 3 (p=0.002), 1 and 4 (p<0.001) and 2 and 4 (p=0.022). The mean hospital stay was 7.08, 4.76, 4.88 and 4.20 days, with a difference between groups 1 and 2 (p<0.001), 1 and 3 (p<0.001) and 1 and 4 (p<0.001). Clinical and radiological improvements were observed in 98.9% of patients. One patient presented with recurrent obstruction. CONCLUSIONS: Our results demonstrate a high success rate with low complication rates. A significant decrease in hospital stay and surgical time was evident after 25 cases.

Postgraduate course in minimally invasive urological surgery.

BACKGROUND: Minimally invasive surgeries are increasingly common as the first option for most urological diseases. However, laparoscopic techniques are difficult to master, especially for surgeons who were not trained during their residency programs. Therefore, postgraduate courses are important for such matters. This study aims to evaluate the results of postgraduate courses in minimally invasive urological surgery. METHODS: A specific questionnaire was used to evaluate the impact of the course on urologists' professional activities. The questionnaire also evaluated demographic data and previous surgical experience. The postgraduate course was divided into 10 monthly modules, each one with 36 hours of activities, from March to December. All students of the laparoscopic postgraduate course from the last five years were enrolled in the study. RESULTS: Forty-one students were included in the study. Thirty-nine students were male (95.1%), and the mean age was 39.5 years (range, 30-60 years). Students from all regions of the country were enrolled. Thirty (73.2%) students had minor laparoscopic experience. All students improved their laparoscopic skills and were able to include new procedures in their daily surgical practice. Eleven students (26.8%) had no laparoscopic experience, and all of them started to perform laparoscopic procedures. The median level of impact on professional life was 75 points (range, 0-100 points). CONCLUSIONS: The postgraduate course is an appropriate way to acquire urological laparoscopic skills. The annual course allowed improvement and initiation of laparoscopic procedures, which significantly impacted urologists' daily activities.

The role of urinary KIM-1, NGAL, CA19-9 and ß2-microglobulin in the assessment of ureteropelvic junction obstruction in adults.

PURPOSE: The objective of this study is to evaluate the diagnostic properties of urinary biomarkers in adults with ureteropelvic junction obstruction: KIM-1, NGAL, CA19-9, and ß2-microglobulin. We also assessed urinary biomarker concentrations following pyeloplasty. MATERIAL AND METHODS: We prospectively studied adults from December 2013 to February 2015. We included 47 patients with a mean age of 38.6 ± 12.7 years. Each patient provided four samples of voided urine for biomarker measurement, one at pre-operative consultation and the others at 1, 3, and 6 months of post-operative follow-up. The control group consisted of 40 healthy individuals with no hydronephrosis on ultrasound evaluation. RESULTS: KIM-1 had an area under the curve of 0.79 (95% CI 0.70-0.89), NGAL 0.71 (95% CI 0.61-0.83), CA19-9 0.70 (95% CI 0.60-0.81), and ß2-microgloblin 0.61 (95% CI 0.50-0.73). KIM-1 was the most sensitive marker with a cut-off of 170.4 pg/mg creatinine (sensitivity 91.4%, specificity 59.1%), whereas CA19-9 was the most specific with a cut-off of 51.3 U/mg creatinine (sensitivity 48.9%, specificity 88.0%). Urinary concentrations of biomarkers decreased after pyeloplasty. CONCLUSIONS: The evaluation of urinary biomarkers is useful in adults undergoing pyeloplasty. KIM-1, NGAL, and CA19-9 were elevated and significantly decreased after surgery.

Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer.

Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC.

Effect of Exercise Training and Testosterone Replacement on Skeletal Muscle Wasting in Patients With Heart Failure With Testosterone Deficiency.

OBJECTIVE: To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in patients with heart failure (HF) with testosterone deficiency. PATIENTS AND METHODS: From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis. RESULTS: Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group. CONCLUSION: Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency.