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1.  Nomogram to predict uric acid kidney stones based on patient’s age, BMI and 24-hour urine profiles: A multicentre validation 
We performed a multicentre validation of a nomogram to predict uric acid kidney stones in two populations.
We reviewed the kidney stone database of two institutions, searching for patients with kidney stones who had stone composition analysis and 24-hour urine collection from January 2010 to December 2013. A nomogram to predict uric acid kidneys stones based on patient age, body mass index (BMI), and 24-hour urine collection was tested. Receiver-operating curves (ROC) were performed.
We identified 445 patients, 355 from Cleveland, United States, and 90 from Sao Paulo, Brazil. Uric acid stone formers were 7.9% and 8.9%, respectively. Uric acid patients had a significantly higher age and BMI, as well as significant lower urinary calcium than calcium stone formers in both populations. Uric acid had significantly higher total points when scored according to the nomogram. ROC curves showed an area under the curve of 0.8 for Cleveland and 0.92 for Sao Paulo. The cutoff value that provided the highest sensitivity and specificity was 179 points and 192 for Cleveland and Sao Paulo, respectively. Using 180 points as a cutoff provided a sensitivity and specificity of 87.5% and 68% for Cleveland, and 100% and 42% for Sao Paulo. Higher cutoffs were associated with higher specificity. The main limitation of this study is that only patients from high volume hospitals with uric acid or calcium stones were included.
Predicting uric acid kidneys stone based on a nomogram, which includes only demographic data and 24-hour urine parameters, is feasible with a high degree of accuracy.
PMCID: PMC4455636  PMID: 26085876
2.  Controlling RECK miR21 Promotes Tumor Cell Invasion and Is Related to Biochemical Recurrence in Prostate Cancer 
Journal of Cancer  2015;6(3):292-301.
The search for biomarkers to characterize prostate cancer aggressiveness has been the objective for the majority of researchers involved with the most prevalent tumor in men. MiRNAs are important for the control of many cellular functions and their deregulation is involved with tumor development and progression. To find miRNAs differentially expressed in prostate cancer and their relation to prognostic factors and biochemical recurrence we studied 53 surgical specimens from men who underwent radical prostatectomy, through a microarray analysis using the microarray platform (GeneChip® miRNA Array - Affymetrix) with more than 46,000 probes and 847 mature human miRNAs and transcripts. We defined different as an expression level greater or less than 1.1 with p<0.05. The validation study using qRT-PCR had confirmed miR21 as overexpressed in tumor that have recurred with a risk of 2.5. Transfection of miR-21 using lipid based assay in DU145 cell line, showed decrease in expression of RECK resulting in increase in expression of MMP9. Invasion assay with Matrigel showed increase in tumor cell invasion after miR-21 transfection. We conclude that miR-21 overexpression is related to increased biochemical recurrence after surgical treatment of prostate cancer. And the negative control of RECK results in overexpression of MMP9 promotes increasing tumor cell invasion supporting miR-21 as an oncomiR related to aggressiveness in prostate cancer.
PMCID: PMC4317766  PMID: 25663948
Prostate cancer; Micro RNA; Microarray; Biochemical recurrence; Prognosis; miR-21; Cell invasion; RECK; DU145
3.  Neurological status predicts response to alpha-blockers in men with voiding dysfunction and Parkinson's disease 
Clinics  2014;69(12):817-822.
To evaluate predictors of the response to doxazosin, a selective alpha-adrenoceptor antagonist, when used for the treatment of lower urinary tract symptoms in men with Parkinson's disease.
In a prospective study, 33 consecutive men (mean age 59.2±7.0 years) with Parkinson's disease and lower urinary tract symptoms were evaluated. Neurological dysfunction was assessed with the Unified Parkinson's Disease Rating Scale. Urological assessment was performed at baseline and after 12 weeks of treatment with 4 mg/day of extended-release doxazosin, including symptom evaluation with the International Continence Society male short-form questionnaire, an assessment of the impact of lower urinary tract symptoms on quality of life and urodynamics. Clinical and urodynamic predictors of response were specifically evaluated.
Compared with the score at baseline, the total International Continence Society male short-form score was reduced after doxazosin administration, from 17.4±7.5 to 11.1±6.9 (p<0.001). The impact of lower urinary tract symptoms on quality of life was also significantly reduced, from 1.8±1.1 to 1.0±1.0 (p<0.001) and the maximum urinary flow varied from 9.3±4.4 to 11.2±4.6 ml/s (p = 0.025). The severity of neurological impairment was the only predictor of the clinical response. Additionally, patients with a Unified Parkinson's Disease Rating Scale score lower than 70 had a significantly higher chance of clinical improvement with doxazosin treatment than those with higher Unified Parkinson's Disease Rating Scale scores did (RR = 3.10, 95% CI = [1.15 to 5.37], p = 0.011).
Doxazosin resulted in the improvement of lower urinary tract symptoms and the maximum flow rate and was well tolerated in men with Parkinson's disease. The response to treatment is dependent on the severity of neurological disability.
PMCID: PMC4286669  PMID: 25627993
Lower Urinary Tract Symptoms; Parkinson's Disease; Urodynamics; Doxazosin
4.  The involvement of miR-100 in bladder urothelial carcinogenesis changing the expression levels of mRNA and proteins of genes related to cell proliferation, survival, apoptosis and chromosomal stability 
MicroRNAs (miRNA) are small non-coding RNAs that play an important role in the control of gene expression by inhibiting protein translation or promoting messenger RNA degradation. Today, miRNAs have been shown to be involved in various physiological and pathological cellular processes, including cancer, where they can act as oncogenes or tumor suppressor genes. Recently, lowered expression of miR-100, resulting in upregulation of FGFR3, has been correlated with low-grade, non-invasive bladder urothelial cancer, as an alternative oncogenesis pathway to the typical FGFR3 gene mutation. Our aim is to analyze the role of miR-100 in bladder cancer cell lines in controlling the expression of some of its possible target genes, including FGFR3 and its relationship with proliferation, apoptosis and DNA ploidy.
The bladder cancer cell lines RT4 and T24 were transfected with pre-miR 100, anti-miR 100 and their respective controls using a lipid-based formulation. After transfection mRNA and protein levels of its supposed target genes THAP2, BAZ2A, mTOR, SMARCA5 and FGFR3 were analyzed by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. Cell proliferation, apoptosis and DNA ploidy were analyzed by flow cytometry. For statistical analysis, a t-test was applied, p < 0.05 was considered significant.
After miR-100 transfection, there was a significant reduction in the mRNA of mTOR (p = 0.006), SMARCA5 (p = 0.007) and BAZ2A (p = 0.029) in RT4, mTOR (p = 0.023) and SMARCA5 (p = 0.015) in T24. There was a reduction in the expression of all proteins, variable from 22.5% to 57.1% in both cell lines. In T24 miR-100 promoted an increase in cell proliferation and anti-miR 100 promoted apoptosis characterizing miR-100 as an oncomiR in this cell line representative of a high-grade urothelial carcinoma.
miR-100 transfection reduces expression of BAZ2A, mTOR and SMARCA5 mRNA and protein in BC cell lines. miR-100 would be classified as an oncomiR in T24 cells representative of high grade urothelial carcinoma promoting increase in cell proliferation and reduction in apoptosis. The knowledge of miRNA role in tumors will allow their use as tumor markers and targets for new therapies.
PMCID: PMC4260205  PMID: 25493074
Bladder cancer; MicroRNA; miR-100; Gene expression; Protein expression; PCR; Western blotting
5.  Comprehensive Study of Gene and microRNA Expression Related to Epithelial-Mesenchymal Transition in Prostate Cancer 
PLoS ONE  2014;9(11):e113700.
Prostate cancer is the most common cancer in men, and most patients have localized disease at the time of diagnosis. However, 4% already present with metastatic disease. Epithelial-mesenchymal transition is a fundamental process in carcinogenesis that has been shown to be involved in prostate cancer progression. The main event in epithelial-mesenchymal transition is the repression of E-cadherin by transcription factors, but the process is also regulated by microRNAs. The aim of this study was to analyze gene and microRNA expression involved in epithelial-mesenchymal transition in localized prostate cancer and metastatic prostate cancer cell lines and correlate with clinicopathological findings. We studied 51 fresh frozen tissue samples from patients with localized prostate cancer (PCa) treated by radical prostatectomy and three metastatic prostate cancer cell lines (LNCaP, DU145, PC3). The expression of 10 genes and 18 miRNAs were assessed by real-time PCR. The patients were divided into groups according to Gleason score, pathological stage, preoperative PSA, biochemical recurrence, and risk group for correlation with clinicopathological findings. The majority of localized PCa cases showed an epithelial phenotype, with overexpression of E-cadherin and underexpression of the mesenchymal markers. MiRNA-200 family members and miRNAs 203, 205, 183, 373, and 21 were overexpressed, while miRNAs 9, 495, 29b, and 1 were underexpressed. Low-expression levels of miRNAs 200b, 30a, and 1 were significantly associated with pathological stage. Lower expression of miR-200b was also associated with a Gleason score ≥8 and shorter biochemical recurrence-free survival. Furthermore, low-expression levels of miR-30a and high-expression levels of Vimentin and Twist1 were observed in the high-risk group. Compared with the primary tumor, the metastatic cell lines showed significantly higher expression levels of miR-183 and Twist1. In summary, miRNAs 200b, 30a, 1, and 183 and the genes Twist1 and Vimentin might play important roles in the progression of prostate cancer and may eventually become important prognostic markers.
PMCID: PMC4237496  PMID: 25409297
6.  Nocturia is the Lower Urinary Tract Symptom With Greatest Impact on Quality of Life of Men From a Community Setting 
Lower urinary tract symptoms are numerous, but the specific impact of each of these symptoms on the quality of life (QoL) has not been evaluated in community-dwelling men. An assessment of these symptoms and their effects on QoL was the focus of this study.
We performed a cross-sectional study with 373 men aged >50 years from a community setting. Patients completed the International Prostate Symptom Score questionnaire, which includes questions on each of the specific urinary symptoms and a question addressing health-related QoL that are graded from 0 to 5. We used the Pearson correlation test to assess the impact of each symptom on QoL.
Nocturia (58.9%) was the most prevalent urinary symptom. The mean score was 0.9±1.4 for incomplete emptying, 1.0±1.5 for frequency, 0.9±1.3 for intermittency, 0.8±1.3 for urgency, 1.0±1.5 for weak stream, 0.5±1.0 for straining, and 2.0±1.6 for nocturia. Nocturia and frequency were the only symptoms associated with poorer QoL, with nocturia showing a stronger association.
Nocturia affects 50% of community dwelling men aged >50 years, and is the lower urinary tract symptom with the greatest negative impact on QoL.
PMCID: PMC4076485  PMID: 24987561
Epidemiology; Lower urinary tract symptoms; Nocturia; Prostatic hyperplasia; Quality of life
7.  Adhesion molecules of detrusor muscle cells are influenced by a hypercholesterolemic diet or bladder outlet obstruction in a wistar rat model 
BMC Urology  2013;13:50.
Cell adhesion molecules (CAMs) are essential for maintaining tissue integrity by regulating intercellular and cell to extracellular matrix interactions. Cadherins and catenins are CAMs that are located on the cell membrane and are important for adherens junction (AJ) function. This study aims to verify if hypercholesterolemic diet (HCD) or bladder outlet obstruction (BOO) promotes structural bladder wall modifications specific to alterations in the expression of cadherins and catenins in detrusor muscle cells.
Forty-five 4-week-old female Wistar rats were divided into the following three groups: group 1 was a control group that was fed a normal diet (ND); group 2 was the BOO model and was fed a ND; and group 3 was a control group that was fed a HCD (1.25% cholesterol). Initially, serum cholesterol, LDL cholesterol and body weight were determined. Four weeks later, groups 1 and 3 underwent a sham operation; whereas group 2 underwent a partial BOO procedure that included a suture tied around the urethra. Six weeks later, all rats had their bladders removed, and previous exams were repeated. The expression levels of N-, P-, and E-cadherin, cadherin-11 and alpha-, beta- and gamma-catenins were evaluated by immunohistochemistry with a semiquantitative analysis.
Wistar rats fed a HCD (group 3) exhibited a significant increase in LDL cholesterol levels (p=0.041) and body weight (p=0.017) when compared to both groups that were fed a normal diet in a ten-week period. We found higher β- and γ-catenin expression in groups 2 and 3 when compared to group 1 (p = 0.042 and p = 0.044, respectively). We also observed Cadherin-11 overexpression in group 3 when compared to groups 1 and 2 (p = 0.002).
A HCD in Wistar rats promoted, in addition to higher body weight gain and increased serum LDL cholesterol levels, overexpression of β- and γ-catenin in the detrusor muscle cells. Similar finding was observed in the BOO group. Higher Cadherin-11 expression was observed only in the HCD-treated rats. These findings may be associated with bladder dysfunctions that occur under such situations.
PMCID: PMC3817818  PMID: 24139451
Cell adhesion molecules; Bladder dysfunction; Hypercholesterolemic diet; Bladder outlet obstruction
8.  Long-term Treatment Outcomes Between Surgical Correction and Conservative Management for Penile Fracture: Retrospective Analysis 
Korean Journal of Urology  2013;54(7):472-476.
Early surgical management is the standard of care for penile fracture. Conservative treatment is an option with recent reports revealing lower success rates. We reviewed the data and long-term outcomes of patients with penile injury submitted to surgical or conservative treatment.
Materials and Methods
Between January 2004 and February 2012, 42 patients with penile blunt trauma on an erect penis were admitted to our center. We analyzed the following variables: age, etiology, symptoms and signs, diagnostic tests, treatment used, complications and erectile function during the follow-up. One patient was excluded due to missing information. Thirty-five patients underwent surgical repair and 6 patients were submitted to conservative management.
Mean follow-up was 19.2 months (range, 7 days to 72 months). The mean elapsed time from trauma to surgery was 21.3±12.5 hours. Trauma during sexual relationship was the main cause (80.9%) of penile fracture. Urethral injury was present in five patients submitted to surgery. Dorsal vein injury occurred in three patients with false penile fracture and concomitant spongious corpus lesion was present in three patients. During follow-up, 31 cases (88.6%) of the surgical group and four cases (66.7%) of the conservative group reported sufficient erections for intercourse, with no voiding dysfunction and no penile curvature. However, the remaining two patients (33.3%) from the conservative group developed erectile dysfunction and three patients (50%) developed penile deviation.
Surgical approach provides excellent functional outcomes and lower complications. Early surgical management of penile fracture provides superior results and conservative approach should be avoided.
PMCID: PMC3715712  PMID: 23878691
Penis; Surgery; Therapy; Wounds and injuries
9.  MicroRNA 100: a context dependent miRNA in prostate cancer 
Clinics  2013;68(6):797-802.
MicroRNAs are noncoding RNA molecules involved in the development and progression of tumors. We have found that miRNA-100 is underexpressed in metastatic prostate cancer compared to localized disease. Conversely higher levels of miR-100 are related to biochemical recurrence after surgery. This suggests that miR-100 may be a context-dependent miRNA, acting as oncogene or tumor suppressor miRNA. Our aim is to demonstrate the role of miR-100 in the control of predicted target genes in prostate cancer cell lines.
Cell lines DU145 and PC3 were transfected with miR-100, antimiR-100 and after 24 h and 48 h of exposure, qRT-PCR and western blot were performed for mTOR, FGFR3, THAP2, SMARCA5 and BAZ2A.
There was reduction in mTOR (p = 0.025), THAP2 (p = 0.038), SMARCA5 (p = 0.001) and BAZ2A (p = 0.006) mRNA expression in DU145 cells after exposure to miR-100. In PC3 cells, mTOR expression was decreased by miR-100 (p = 0.01). There was a reduction in the expression levels of proteins encoded by studied genes, ranging from 34% to 69%.
We demonstrate that miR-100 is a context-dependent miRNA controlling BAZ2, mTOR, FGFR3, SMARCA5 and THAP2 that might be involved in PC progression. The elucidation of the roles of miRNAs in tumors is important because they can be used as therapeutic targets in the future.
PMCID: PMC3674267  PMID: 23778488
Prostate Cancer; Micro RNA; miR-100; Gene Expression; Protein Expression; PCR; Western Blot
10.  Predicting calyceal access for percutaneous nephrolithotomy with computed tomography multiplanar reconstruction 
Clinics  2013;68(6):892-895.
Objective parameters in computed tomography (CT) scans that could predict calyceal access during percutaneous nephrolithotomy have not been evaluated. These parameters could improve access planning for percutaneous nephrolithotomy. We aimed to determine which parameters extracted from a preoperative multiplanar reconstructed CT could predict renal calyceal access during a percutaneous nephrolithotomy.
From January 2009 through April 2011, 230 patients underwent 284 percutaneous nephrolithotomies at our institution. Sixteen patients presented with complete staghorn calculi, and 11 patients (13 renal units) were analyzed. Five parameters were extracted from a preoperative reconstructed CT and compared with the surgical results of percutaneous nephrolithotomy.
Fifty-eight calyces were studied, with an average of 4.4 calyces per procedure. A rigid nephroscope was used to access a particular calyx, and a univariate analysis showed that the entrance calyx had a smaller length (2.7 vs. 3.98 cm, p = 0.018). The particular calyx to be accessed should have a smaller length (2.22 vs. 3.19 cm, p = 0.012), larger angles (117.6 vs. 67.96, p<0.001) and larger infundibula (0.86 vs. 0.61 cm, p = 0.002). In the multivariate analysis, the only independent predictive factor for accessing a particular calyx was the angle between the entrance calyx and the calyx to be reached (OR 1.15, 95% confidence interval [CI], 1.053–1.256, p = 0.002).
The angle between calyces obtained by multiplanar CT reconstruction is the only predictor of calyx access.
PMCID: PMC3674302  PMID: 23778484
Computed Tomography; Kidney; Percutaneous Nephrolithotomy; Urinary Calculi
11.  The role of micro RNAs let7c, 100 and 218 expression and their target RAS, C-MYC, BUB1, RB, SMARCA5, LAMB3 and Ki-67 in prostate cancer 
Clinics  2013;68(5):652-657.
The aim of this study is to verify the expression of proteins that are controlled by miR-let7c, 100 and 218 using immunohistochemistry in tissue microarray representative of localized and metastasized the lymph nodes and bone prostate cancer.
To verify the expression of proteins that are controlled by miR-let7c (C-MYC, BUB1, RAS) 100 (SMARCA5, RB) and 218 (LAMB3) and cell proliferation (Ki-67) we used immunohistochemistry and computerized image system ImageJ MacBiophotonics in three tissue microarrays representative of localized prostate cancer and lymph node and bone metastases. miRNA expression was evaluated by qRT-PCR using 60 paraffin blocks to construct the tissue microarray representative of localized disease.
RAS expression was increased in localized prostate cancer and bone metastases compared to the lymph nodes (p = 0.017). RB showed an increase in expression from localized prostate cancer to lymph node and bone metastasis (p = 0.036). LAMB3 was highly expressed in localized and lymph node metastases (p<0.001). Cell proliferation evaluated by Ki-67 showed an increase from localized prostate cancer to metastases (p<0.001). We did not found any relationship between C-MYC (p = 0.253), BUB1 (p = 0.649) and SMARCA5 (p = 0.315) protein expression with prognosis or tumor behavior.
We found that the expression of RAS, RB, LAMB3 and Ki-67 changed in the different stages of prostate cancer. Furthermore, we confirmed the overexpression of the miRNAs let7c, 100 and 218 in localized prostate cancer but failed to show the control of protein expression by the putative controller miRNAs using immunohistochemistry.
PMCID: PMC3654318  PMID: 23778407
Prostate Cancer; Prognosis; Tumor Markers; Micro RNA; Immunohistochemistry; RAS; C-MYC; BUB1; SMARCA5; LAMB3; Ki-67, RB
12.  Prima-1 induces apoptosis in bladder cancer cell lines by activating p53 
Clinics  2013;68(3):297-303.
Bladder cancer represents 3% of all carcinomas in the Brazilian population and ranks second in incidence among urological tumors, after prostate cancer. The loss of p53 function is the main genetic alteration related to the development of high-grade muscle-invasive disease. Prima-1 is a small molecule that restores tumor suppressor function to mutant p53 and induces cancer cell death in various cancer types. Our aim was to investigate the ability of Prima-1 to induce apoptosis after DNA damage in bladder cancer cell lines.
The therapeutic effect of Prima-1 was studied in two bladder cancer cell lines: T24, which is characterized by a p53 mutation, and RT4, which is the wild-type for the p53 gene. Morphological features of apoptosis induced by p53, including mitochondrial membrane potential changes and the expression of thirteen genes involved in apoptosis, were assessed by microscopic observation and quantitative real-time PCR (qRT-PCR).
Prima-1 was able to reactivate p53 function in the T24 (p53 mt) bladder cancer cell line and promote apoptosis via the induction of Bax and Puma expression, activation of the caspase cascade and disruption of the mitochondrial membrane in a BAK-independent manner.
Prima-1 is able to restore the transcriptional activity of p53. Experimental studies in vivo may be conducted to test this molecule as a new therapeutic agent for urothelial carcinomas of the bladder, which characteristically harbor p53 mutations.
PMCID: PMC3611750  PMID: 23644847
Bladder cancer; p53; Apoptosis; Prima-1
13.  Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: Analysis of 100 cases from a high-volume urologic center 
Clinics  2012;67(12):1415-1418.
In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center.
We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment.
Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostate-specific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer.
Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.
PMCID: PMC3521804  PMID: 23295595
Prostatic Hyperplasia; Prostatectomy; Transurethral Resection of Prostate; Aged; Quality of Life, Complications
14.  Laparoscopic Testicular Preservation in Adults with Intra-Abdominal Cryptorchidism: Is It Beneficial? 
Advances in Urology  2012;2012:329237.
Purpose. To present the results in a midterm followup of laparoscopic testicular preservation in adults with intra-abdominal cryptorchidism. Methods. We analyzed 14 adult patients with cryptorchidism (19 testes) submitted to transabdominal laparoscopic evaluation and treatment of the condition. Data was collected retrospectively from a prospective database from August 2005 to May 2010. It analyzed patient age, affected side, procedure, mean operative time, mean hospital stay, postoperative testis position, intra- and postoperative complications, presence of malignancy in the removed testis, and midterm outcomes: size of the testis, development of tumors, and fertility. Results. Mean patient age was 29 (18–54) years. Thirteen (68.4%) testes were preserved. There were no intra- or postoperative complications. After a mean followup of 48.7 (20–64) months, all patients submitted to orchiopexy had the organs correctly positioned, although 2 testes were significantly smaller than before the procedure. No patient presented any signs of malignancy during the followup. Fertility was not preserved in bilateral cases. Conclusion. Laparoscopic testicular evaluation and eventual preservation are feasible and safe. In a midterm followup, testicular tumor is not a concern, and unfortunately, fertility may not be preserved in bilateral cases.
PMCID: PMC3512247  PMID: 23227040
15.  Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study 
Recent studies have demonstrated that pathological analysis of retroperitoneal residual masses of patients with testicular germ cell tumors revealed findings of necrotic debris or fibrosis in up to 50% of patients. We aimed at pursuing a clinical and pathological review of patients undergoing post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in order to identify variables that may help predict necrosis in the retroperitoneum.
We performed a retrospective analysis of all patients who underwent PC-RPLND at the University Hospital of the University of São Paulo and Cancer Institute of Sao Paulo between January 2005 and September 2011. Clinical and pathological data were obtained and consisted basically of: measures of retroperitoneal masses, histology of the orchiectomy specimen, serum tumor marker and retroperitoneal nodal size before and after chemotherapy.
We gathered a total of 32 patients with a mean age of 29.7; pathological analysis in our series demonstrated that 15 (47%) had necrosis in residual retroperitoneal masses, 15 had teratoma (47%) and 2 (6.4%) had viable germ cell tumors (GCT). The mean size of the retroperitoneal mass was 4.94 cm in our sample, without a difference between the groups (P = 0.176). From all studied variables, relative changes in retroperitoneal lymph node size (P = 0.04), the absence of teratoma in the orchiectomy specimen (P = 0.03) and the presence of choriocarcinoma in the testicular analysis after orchiectomy (P = 0.03) were statistically significant predictors of the presence of necrosis. A reduction level of 35% was therefore suggested to be the best cutoff for predicting the absence of tumor in the retroperitoneum with a sensitivity of 73.3% and specificity of 82.4%.
Even though retroperitoneal lymph node dissection remains the gold standard for patients with residual masses, those without teratoma in the primary tumor and a shrinkage of 35% or more in retroperitoneal mass have a considerably smaller chance of having viable GCT or teratoma in the retroperitoneum and a surveillance program could be considered.
PMCID: PMC3502267  PMID: 23021209
Testicular cancer; Retroperitoneal lymph node dissection; Necrosis; Teratoma
16.  Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration 
European urology  2011;60(2):205-210.
Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined.
To identify predictors of biochemical recurrence (BCR), metastasis, and death following SRP to help select patients who may benefit from SRP.
Design, setting, and participants
This is a retrospective, international, multi-institutional cohort analysis. There was a median follow-up of 4.4 yr following SRP performed on 404 men with radiation-recurrent PCa from 1985 to 2009 in tertiary centers.
Open SRP.
BCR after SRP was defined as a serum prostate-specific antigen (PSA) ≥0.1 or ≥0.2 ng/ml (depending on the institution). Secondary end points included progression to metastasis and cancer-specific death.
Results and limitations
Median age at SRP was 65 yr of age, and median pre-SRP PSA was 4.5 ng/ml. Following SRP, 195 patients experienced BCR, 64 developed metastases, and 40 died from PCa. At 10 yr after SRP, BCR-free survival, metastasis-free survival, and cancer-specific survival (CSS) probabilities were 37% (95% confidence interval [CI], 31–43), 77% (95% CI, 71–82), and 83% (95% CI, 76–88), respectively. On preoperative multivariable analysis, pre-SRP PSA and Gleason score at postradiation prostate biopsy predicted BCR (p = 0.022; global p < 0.001) and metastasis (p = 0.022; global p < 0.001). On postoperative multivariable analysis, pre-SRP PSA and pathologic Gleason score at SRP predicted BCR (p = 0.014; global p < 0.001) and metastasis (p < 0.001; global p < 0.001). Lymph node involvement (LNI) also predicted metastasis (p = 0.017). The main limitations of this study are its retrospective design and the follow-up period.
In a select group of patients who underwent SRP for radiation-recurrent PCa, freedom from clinical metastasis was observed in >75% of patients 10 yr after surgery. Patients with lower pre-SRP PSA levels and lower postradiation prostate biopsy Gleason score have the highest probability of cure from SRP.
PMCID: PMC3124574  PMID: 21420229
Prostate cancer; Radiation therapy; Salvage therapy
17.  Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer 
BMC Urology  2012;12:18.
Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC).
MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia.
MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005).
We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.
PMCID: PMC3424138  PMID: 22695075
Bladder cancer; Matrix metalloproteinase; Prognosis; Diagnosis; Gene expression
18.  Cranberries and lower urinary tract infection prevention 
Clinics  2012;67(6):661-667.
Lower urinary tract infections are very common diseases. Recurrent urinary tract infections remain challenging to treat because the main treatment option is long-term antibiotic prophylaxis; however, this poses a risk for the emergence of bacterial resistance. Some options to avoid this risk are available, including the use of cranberry products. This article reviews the key methods in using cranberries as a preventive measure for lower urinary tract infections, including in vitro studies and clinical trials.
PMCID: PMC3370320  PMID: 22760907
Urinary Tract Infection; Cranberry; Cystitis; Prevention
19.  miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer 
BMC Urology  2012;12:14.
Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line.
Materials and methods
To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR).
The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025).
Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.
PMCID: PMC3431982  PMID: 22642976
Prostate cancer; Prognosis; RECK; Micro RNA; Metaloproteinases
20.  Metabolic assessment of elderly men with urolithiasis 
Clinics  2012;67(5):457-461.
To assess the presence of metabolic disorders in elderly men with urolithiasis.
We performed a case-control study. The inclusion criteria were as follows: (1) men older than 60 years of age and either (2) antecedent renal colic or an incidental diagnosis of urinary lithiasis after age 60 (case arm) or (3) no antecedent renal colic or incidental diagnosis of urolithiasis (control arm). Each individual underwent an interview, and those who were selected underwent all clinical protocol examinations: serum levels of total and ionized calcium, uric acid, phosphorus, glucose, urea, creatinine and parathyroid hormone, urine culture, and analysis of 24-hour urine samples (levels of calcium, citrate, creatinine, uric acid and sodium, pH and urine volume). Each case arm patient underwent two complete metabolic urinary investigations, whereas each control arm individual underwent one examination. NCT01246531.
A total of 51 subjects completed the clinical investigation: 25 in the case arm and 26 in the control arm. In total, 56% of the case arm patients had hypocitraturia (vs. 15.4% in the control arm; p = 0.002). Hypernatriuria was detected in 64% of the case arm patients and in 30.8% of the controls (p = 0.017).
Hypocitraturia and hypernatriuria are the main metabolic disorders in elderly men with urolithiasis.
PMCID: PMC3351268  PMID: 22666789
Urolithiasis; Calculi; Citrate; Metabolism; Aging; Elderly
21.  Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model 
Clinics  2011;66(12):2121-2124.
Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer.
Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA.
Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model.
Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.
PMCID: PMC3226609  PMID: 22189739
Bladder cancer; Treatment; Curcumin, Prima-1; Apoptosis
22.  Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer 
Clinics  2011;66(7):1143-1147.
To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer.
TGF-β1 expression levels were analyzed using the quantitative real-time polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen malignant and benign tissue specimens collected from 89 patients who had clinically localized prostate cancer and had been treated with radical prostatectomy. The control group consisted of 11 patients with benign prostate hyperplasia. The expression levels of TGF-β1 were compared between the groups in terms of Gleason scores, pathological staging, and prostate-specific antigen serum levels.
In the majority of the tumor samples, TGF-β1 was underexpressed 67.0% of PCa patients. The same expression pattern was identified in benign tissues of patients with prostate cancer. Although most cases exhibited underexpression of TGF-β1, a higher expression level was found in patients with Gleason scores ≥7 when compared to patients with Gleason scores <7 (p = 0.002). Among the 26 cases of TGF-β1 overexpression, 92.3% had poor prognostic features.
TGF-β1 was underexpressed in prostate cancers; however, higher expression was observed in tumors with higher Gleason scores, which suggests that TGF-β1 expression may be a useful prognostic marker for prostate cancer. Further studies of clinical specimens are needed to clarify the role of TGF-β1 in prostate carcinogenesis.
PMCID: PMC3148455  PMID: 21876965
Prostate cancer; Prognosis; Molecular markers; TGF-β
24.  Comparison between two shock wave regimens using frequencies of 60 and 90 impulses per minute for urinary stones 
Clinics  2010;65(10):961-965.
Two different regimens of SWL delivery for treating urinary stones were compared.
Patients with urinary stones were randomly divided into two groups, one of which received 3000 shocks at a rate of 60 impulses per minute and the other of which received 4000 shocks at 90 impulses per minute. Success was defined as stone‐free status or the detection of residual fragments of less than or equal to 3 mm three months after treatment. Partial fragmentation was considered to have occurred if a significant reduction in the stone burden was observed but residual fragments of 3mm or greater remained.
A total of 143 procedures were performed with 3000 impulses at a rate of 60 impulses per minute, and 156 procedures were performed with 4000 impulses at 90 impulses per minute. The stone‐free rate was 53.1% for patients treated with the first regimen and 54.8% for those treated with the second one (p =  0.603). The stone‐free rate for stones smaller than 10 mm was 60% for patients treated with 60 impulses per minute and 58.6% for those treated with 90 impulses per minute. For stones bigger than 10 mm, stone‐free rates were 34.2% and 45.7%, respectively (p = 0.483). Complications occurred in 2.3% of patients treated with 60 impulses per minute and 3.3% of patients treated with 90 impulses per minute.
No significant differences in the stone‐free and complication rates were observed by reducing the total number of impulses from 4000 to 3000 and the frequency from 90 to 60 impulses per minute.
PMCID: PMC2972613  PMID: 21120294
Kidney calculi; Urolithiasis; Urologic surgical procedures; Extracorporeal shockwave lithotripsy
25.  Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients 
Symptomatic benign prostatic hyperplasia (BPH) typically occurs in the sixth and seventh decades, and the most frequent obstructive urinary symptoms are hesitancy, decreased urinary stream, sensation of incomplete emptying, nocturia, frequency, and urgency. Various medications, specifically 5-α-reductase inhibitors and selective α-blockers, can decrease the severity of the symptoms secondary to BPH, but prostatectomy is still considered to be the traditional method of management. We report the preliminary results for two patients with acute urinary retention due to BPH, successfully treated by prostate artery embolization (PAE). The patients were investigated using the International Prostate Symptom Score, by digital rectal examination, urodynamic testing, prostate biopsy, transrectal ultrasound (US), and magnetic resonance imaging (MRI). Uroflowmetry and postvoid residual urine volume complemented the investigation at 30, 90, and 180 days after PAE. The procedure was performed under local anesthesia; embolization of the prostate arteries was performed with a microcatheter and 300- to 500-μm microspheres using complete stasis as the end point. One patient was subjected to bilateral PAE and the other to unilateral PAE; they urinated spontaneously after removal of the urethral catheter, 15 and 10 days after the procedure, respectively. At 6-month follow-up, US and MRI revealed a prostate reduction of 39.7% and 47.8%, respectively, for the bilateral PAE and 25.5 and 27.8%, respectively, for the patient submitted to unilateral PAE. The early results, at 6-month follow-up, for the two patients with BPH show a promising potential alternative for treatment with PAE.
PMCID: PMC2841280  PMID: 19908092
Benign prostatic hyperplasia; Prostate; Embolization; Urinary retention; Prostatic artery

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