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1.  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.
Background
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.1186/1471-2490-13-50
PMCID: PMC3817818  PMID: 24139451
Cell adhesion molecules; Bladder dysfunction; Hypercholesterolemic diet; Bladder outlet obstruction
2.  Long-term Treatment Outcomes Between Surgical Correction and Conservative Management for Penile Fracture: Retrospective Analysis 
Korean Journal of Urology  2013;54(7):472-476.
Purpose
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.
Results
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.
Conclusions
Surgical approach provides excellent functional outcomes and lower complications. Early surgical management of penile fracture provides superior results and conservative approach should be avoided.
doi:10.4111/kju.2013.54.7.472
PMCID: PMC3715712  PMID: 23878691
Penis; Surgery; Therapy; Wounds and injuries
3.  MicroRNA 100: a context dependent miRNA in prostate cancer 
Clinics  2013;68(6):797-802.
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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%.
CONCLUSIONS:
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.
doi:10.6061/clinics/2013(06)12
PMCID: PMC3674267  PMID: 23778488
Prostate Cancer; Micro RNA; miR-100; Gene Expression; Protein Expression; PCR; Western Blot
4.  Predicting calyceal access for percutaneous nephrolithotomy with computed tomography multiplanar reconstruction 
Clinics  2013;68(6):892-895.
OBJECTIVES:
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.
METHODS:
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.
RESULTS:
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).
CONCLUSION:
The angle between calyces obtained by multiplanar CT reconstruction is the only predictor of calyx access.
doi:10.6061/clinics/2013(06)27
PMCID: PMC3674302  PMID: 23778484
Computed Tomography; Kidney; Percutaneous Nephrolithotomy; Urinary Calculi
5.  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.
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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.
doi:10.6061/clinics/2013(05)12
PMCID: PMC3654318  PMID: 23778407
Prostate Cancer; Prognosis; Tumor Markers; Micro RNA; Immunohistochemistry; RAS; C-MYC; BUB1; SMARCA5; LAMB3; Ki-67, RB
6.  Prima-1 induces apoptosis in bladder cancer cell lines by activating p53 
Clinics  2013;68(3):297-303.
OBJECTIVES:
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.
METHOD:
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).
RESULTS:
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.
CONCLUSION:
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.
doi:10.6061/clinics/2013(03)OA03
PMCID: PMC3611750  PMID: 23644847
Bladder cancer; p53; Apoptosis; Prima-1
7.  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.
OBJECTIVES:
In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
doi:10.6061/clinics/2012(12)11
PMCID: PMC3521804  PMID: 23295595
Prostatic Hyperplasia; Prostatectomy; Transurethral Resection of Prostate; Aged; Quality of Life, Complications
8.  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.
doi:10.1155/2012/329237
PMCID: PMC3512247  PMID: 23227040
9.  Predicting necrosis in residual mass analysis after retroperitoneal lymph node dissection: a retrospective study 
Background
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.
Methods
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.
Results
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%.
Conclusions
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.
doi:10.1186/1477-7819-10-203
PMCID: PMC3502267  PMID: 23021209
Testicular cancer; Retroperitoneal lymph node dissection; Necrosis; Teratoma
10.  Salvage Radical Prostatectomy for Radiation-recurrent Prostate Cancer: A Multi-institutional Collaboration 
European urology  2011;60(2):205-210.
Background
Oncologic outcomes in men with radiation-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP) are poorly defined.
Objective
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.
Intervention
Open SRP.
Measurements
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.
Conclusions
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.
doi:10.1016/j.eururo.2011.03.011
PMCID: PMC3124574  PMID: 21420229
Prostate cancer; Radiation therapy; Salvage therapy
11.  Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer 
BMC Urology  2012;12:18.
Background
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).
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1471-2490-12-18
PMCID: PMC3424138  PMID: 22695075
Bladder cancer; Matrix metalloproteinase; Prognosis; Diagnosis; Gene expression
12.  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.
doi:10.6061/clinics/2012(06)18
PMCID: PMC3370320  PMID: 22760907
Urinary Tract Infection; Cranberry; Cystitis; Prevention
13.  miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer 
BMC Urology  2012;12:14.
Background
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).
Results
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).
Conclusions
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.
doi:10.1186/1471-2490-12-14
PMCID: PMC3431982  PMID: 22642976
Prostate cancer; Prognosis; RECK; Micro RNA; Metaloproteinases
14.  Metabolic assessment of elderly men with urolithiasis 
Clinics  2012;67(5):457-461.
OBJECTIVE:
To assess the presence of metabolic disorders in elderly men with urolithiasis.
METHODS:
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. ClinicalTrials.gov: NCT01246531.
RESULTS:
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).
CONCLUSION:
Hypocitraturia and hypernatriuria are the main metabolic disorders in elderly men with urolithiasis.
doi:10.6061/clinics/2012(05)09
PMCID: PMC3351268  PMID: 22666789
Urolithiasis; Calculi; Citrate; Metabolism; Aging; Elderly
15.  Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model 
Clinics  2011;66(12):2121-2124.
OBJECTIVE:
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.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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.
doi:10.1590/S1807-59322011001200019
PMCID: PMC3226609  PMID: 22189739
Bladder cancer; Treatment; Curcumin, Prima-1; Apoptosis
16.  Tgf-β1 expression as a biomarker of poor prognosis in prostate cancer 
Clinics  2011;66(7):1143-1147.
OBJECTIVE:
To evaluate the correlation between transforming growth factor beta (TGF-β1) expression and prognosis in prostate cancer.
PATIENTS AND METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
doi:10.1590/S1807-59322011000700004
PMCID: PMC3148455  PMID: 21876965
Prostate cancer; Prognosis; Molecular markers; TGF-β
18.  Comparison between two shock wave regimens using frequencies of 60 and 90 impulses per minute for urinary stones 
Clinics  2010;65(10):961-965.
PURPOSE:
Two different regimens of SWL delivery for treating urinary stones were compared.
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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.
doi:10.1590/S1807-59322010001000006
PMCID: PMC2972613  PMID: 21120294
Kidney calculi; Urolithiasis; Urologic surgical procedures; Extracorporeal shockwave lithotripsy
19.  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.
doi:10.1007/s00270-009-9727-z
PMCID: PMC2841280  PMID: 19908092
Benign prostatic hyperplasia; Prostate; Embolization; Urinary retention; Prostatic artery
20.  Incidence of Histological Prostatitis and Its Correlation with PSA Density 
Clinics (Sao Paulo, Brazil)  2009;64(11):1049-1051.
OBJECTIVE
The aim of this study was to determine the incidence of asymptomatic, histologically proven prostatitis in men with symptoms of benign prostate hyperplasia and to observe the correlation between asymptomatic prostatitis and prostate specific antigen (PSA) density.
INTRODUCTION
The incidence of type IV prostatitis is unknown. There is a tendency to correlate the presence of inflammatory prostatitis with an elevation of PSA.
MATERIALS AND METHODS
From August 2000 to January 2006, 183 patients who underwent surgical treatment for benign prostate hyperplasia as a result of obstructive or irritative symptoms were prospectively studied. In accordance with the histology findings, these patients were divided into two groups: group I included patients with the presence of histological prostatitis and group II included patients with the absence of histological prostatitis. The mean PSA densities were compared.
RESULTS
Histological evidence of prostatitis was observed in 145 patients. In this group, the mean PSA density was 0.136 ± 0.095. In 38 cases, there was no evidence of inflammation upon histological examination of the surgical samples. In these 38 cases, the mean PSA density was 0.126 ± 0.129. No statistically significant differences were detected between the two groups; the p-value is 0.124.
CONCLUSION
Abnormal PSA density should not be attributed to the inflammatory prostatitis process.
doi:10.1590/S1807-59322009001100003
PMCID: PMC2780520  PMID: 19936177
Prostate; Biopsy; Benign prostate hyperplasia; Prostatitis; Prostate specific antigen
21.  Body Composition Alterations, Energy Expenditure and Fat Oxidation in Elderly Males Suffering from Prostate Cancer, Pre and Post Orchiectomy 
Clinics (Sao Paulo, Brazil)  2009;64(8):781-784.
INTRODUCTION
Testosterone is needed for normal male development, muscle strength, bone mineralization, hematopoietic function, and sexual and reproductive functions. The main purpose of androgen deprivation therapy in prostate cancer is to reduce tumor progression, but therapy is often accompanied by significant adverse effects.
OBJECTIVE
This study aimed to determine the effects of androgen deprivation therapy on body composition and resting metabolic rate in patients with prostate cancer.
PATIENTS AND METHODS
A prospective study was performed to evaluate the body composition of 16 elderly males (aged 63–96; median age 71) with prostate cancer scheduled for orchiectomy, one year before and after surgery. Body composition was measured by DEXA, and energy expenditure, fat and carbohydrate oxidation were measured by indirect calorimetry.
RESULTS
Body weight (p=0.01), lean mass (p=0.004), and lipid oxidation (p=0.001) decreased significantly. Carbohydrate oxidation (p=0.02), FSH (p=0.0001) and LH (p=0.0001) levels increased significantly. Changes in fat mass (p=0.06) and bone mineral density (p=0.48) were not significant.
CONCLUSIONS
After 12 months of androgen deprivation therapy, elderly men with metastatic prostate cancer exhibit a decline in lean body mass and lipid oxidation, together with increased carbohydrate oxidation.
doi:10.1590/S1807-59322009000800012
PMCID: PMC2728192  PMID: 19690663
Androgen deprivation; Metastatic prostate cancer; Hormonotherapy side effects; Lean body mass; Lipolysis regulation
22.  Microsurgical Testicular Denervation for the Treatment of Chronic Testicular Pain – Initial Results 
Clinics (Sao Paulo, Brazil)  2009;64(5):393-396.
INTRODUCTION:
Chronic testicular pain remains an important challenge for urologists. Currently, the treatment plan is primarily empirical, with the first approach consisting of clinical measures. However, some patients remain in pain despite a conservative treatment protocol and, for them, it is possible to perform a surgical procedure that involves severing the scrotal and spermatic branches of the genitofemoral and ilioinguinal nerve fibers.
METHODS:
In our institution, 60 patients were evaluated and treated for idiopathic chronic testicular pain between January 2003 and July 2007. Priority was give to clinical treatment, which evolved from simple to more complex measures. Microsurgical treatment was performed on those who experienced no considerable pain relief (10 individuals in our study).
RESULTS:
Over a twenty-four-month follow-up period, 70% of patients showed complete remission and 20% exhibited partial relief from pain.
doi:10.1590/S1807-59322009000500004
PMCID: PMC2694241  PMID: 19488603
Testicular diseases; Pain; Denervation; Microsurgery; Urologic surgical procedures
23.  Evaluation of the expression of integrins and cell adhesion molecules through tissue microarray in lymph node metastases of prostate cancer 
Background:
Integrins and adhesion molecules are responsible for the maintenance of the epithelial phenotype. Cell culture studies have reported the correlation between adhesion molecule expression and prostate carcinoma, but their role in the metastatic process is not yet known. Our aim is to study the expression profiles of these molecules and evaluate their association with the metastatic behavior of prostate adenocarcinoma.
Materials and Methods:
A Tissue Microarray containing two samples from 19 primary tumors and one from their corresponding lymph node metastases was constructed and subjected to immunohistochemical analysis of the expression of integrins, E-cadherin and β and γ-catenins. Within each case, paired analyses were also performed to evaluate gains or losses in metastasis compared to its primary tumor.
Results:
The expression of αv, αvβ3, α2β1 and γ-catenin were abnormal in almost every case. Marked loss of E-cadherin and β4 integrin was found in primary and metastatic lesions. β-catenin was normal in all primary cases and in 94% of metastases. α6 was normal in all primary tumors and metastases. α3 and α3β1 were normal in 32% of primary cases and in 53% and 6% of metastases, respectively. In paired analyses, loss of E-cadherin, β4, αv, α3β1 and αvβ3 was found in 65%, 71%, 59%, 53% and 47% of patients, respectively. Catenins and α2β1 showed maintenance of expression in most of the cases.
Conclusions:
In this preliminary study we have shown that the loss of cell adhesion molecules can be considered a characteristic of the metastatic phenotype in prostate cancer. Larger series should be evaluated in order to confirm our findings.
doi:10.4103/1477-3163.48453
PMCID: PMC2678866  PMID: 19240373
Cell adhesion molecules; integrins; lymph nodes; metastases; prostate cancer
24.  Percutaneous nephrolithotomy: Current concepts 
Percutaneous nephrolithotomy (PNL) is the procedure of choice for large renal stones. Since its introduction in 1976, many aspects of the operative technique and the endoscopic equipments have had constant evolution, increasing the success rates of the procedure. We performed a literature search using Entrez Pubmed from January 2000 to July 2007 concerning PNL and many aspects related to all steps of the procedure.
We could verify that PNL in supine position has been proved as an acceptable option, but more worldwide experience is necessary. Urologists must be trained to gain their own renal tract access. Minipercutaneous PNL still needs equipments improvements for better results. Tubeless PNL is increasing in popularity and different tract sealants have been studied. Medical prevention is proved to be effective against stone recurrence and should be always used after PNL.
Although the evolution of the technique in the last 20 years, urologists must continue to improve their skills and develop new technologies to offer to the patients more and more a safe and effective option to treat large renal stones.
doi:10.4103/0970-1591.44281
PMCID: PMC2684301  PMID: 19468422
Percutaneous nephrolithotomy; tubeless; kidney stone
25.  Comparative and Prospective Analysis of Three Different Approaches for Live-Donor Nephrectomy 
Clinics (Sao Paulo, Brazil)  2009;64(1):23-28.
PURPOSE:
Living donor nephrectomy is usually performed by a retroperitoneal flank incision. Due to the significant morbidity and long recovery time for a flank incision, anterior extra peritoneal sub-costal and transperitoneal video-laparoscopic methods have been described for donor nephrectomy. We prospectively compare the long-term results of donors as well as functional recipients submitted to these three approaches.
MATERIALS AND METHODS:
A total of 107 live donor renal transplantations were prospectively evaluated from May 2001 to January 2004. Donors were compared with regard to operative and warm ischemia time, postoperative pain, analgesic requirements, and complications. Recipients were compared with regard to graft function, acute cellular rejection, surgical complications, and graft and recipient survival.
RESULTS:
The mean operative and warm ischemia times were longer in the video-laparoscopic group (p<0.001), whereas patients of the flank incision group presented more postoperative pain (p=0.035), required more analgesics (p<0.001), had longer hospital stays (p<0.001), and suffered more pain on the 90th day after surgery (p=0.006). In the sub-costal and flank incision groups, there was a larger number of paraesthesias and abdominal wall asymmetries (p<0.001). Recipient groups were demographically comparable and presented similar acute tubular necrosis incidence and delayed graft function. The incidence of acute cellular rejection was higher in the video-laparoscopic and flank incision groups (p=0.013). There was no difference in serum creatinine levels, surgical complications, or recipient or graft survival between groups.
CONCLUSIONS:
The video-laparoscopic and sub-costal approaches proved to be safe, and to provide donor advantages relative to the flank incision approach. Among recipients, the complication rate, graft survival, and recipient survival were similar in all groups.
doi:10.1590/S1807-59322009000100005
PMCID: PMC2671972  PMID: 19142547
Donor nephrectomy; Kidney transplantation; Laparoscopy; Surgical approaches; Outcomes

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