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PURPOSE: Limited high-quality studies have compared robot-assisted laparoscopic prostatectomy (RALP) vs open retropubic radical prostatectomy. We sought to compare their postoperative outcomes in a randomized setting. MATERIALS AND METHODS: In a single center, 354 men with newly diagnosed prostate cancer were assessed for eligibility; 342 were randomized (1:1). The primary outcome was 90-day complication rates. Functional outcomes and quality of life were assessed over 18 months, and oncological outcomes, biochemical recurrence-free survival, and additional treatment over 36 months. RESULTS: From 2014 to 18, 327 patients underwent surgery (retropubic radical prostatectomy = 156, RALP = 171). Complications occurred in 27 (17.3%) vs 19 (11.1%; P = .107). Patients undergoing RALP experienced lower median bleeding (250.0 vs 719.5 mL; P < .001) and shorter hospitalization time. Urinary EPIC (Expanded Prostate Cancer Index Composite) median scores were better for RALP over 18 months, with higher continence rate at 3 months (80.5% vs 64.7%; P = .002), 6 months (90.1% vs 81.6%; P = .036) and 18 months (95.4% vs 78.8%; P < .001). Sexual EPIC and Sexual Health Inventory for Men median scores were higher with RALP up to 12 months, while the potency rate was superior at 3 months (23.9% vs 5.3%; P = .001) and 6 months (30.6% vs 6.9%; P < .001). Quality of life over the 18 months and oncological outcomes over 36 months were not significantly different between arms. CONCLUSIONS: Complications at 90 days were similar. RALP showed superior sexual outcomes at 1 year, improved urinary outcomes at 18 months, and comparable oncological outcomes at 36 months. TRIAL REGISTRATION: Prospective Analysis of Robot-Assisted Surgery; NCT02292914. https://clinicaltrials.gov/ct2/show/NCT02292914?cond=NCT02292914&draw=2&rank=1.
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Laparoscopia , Complicações Pós-Operatórias , Prostatectomia , Neoplasias da Próstata , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Prostatectomia/métodos , Prostatectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Próstata/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoRESUMO
PURPOSE: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. MATERIALS AND METHODS: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. RESULTS: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). CONCLUSIONS: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.
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Neoplasias Renais , Laparoscopia , Humanos , Neoplasias Renais/patologia , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Prostate biopsy is mostly performed through the transrectal route worldwide and infectious complications may occur in up to 7% of cases. Therefore, alternative strategies to decrease infectious complications are needed. Our aim was to evaluate the effectiveness of intrarectal povidone-iodine cleansing plus formalin disinfection of the needle tip in decreasing infectious complications after transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: We conducted a prospective, single-center, phase III trial in patients undergoing transrectal ultrasound guided prostate biopsy randomized 1:1 to rectal mucosa cleansing with gauze soaked in 10% povidone-iodine solution wrapped around the gloved index finger and needle tip disinfection by immersion in a 10% formalin solution before each puncture vs control group. The primary end point was the rate of infectious complications defined as 1 or more of the following events: fever, urinary tract infection, or sepsis. RESULTS: Overall, 633 patients were randomized to the intervention group and 623 to the control group. The infectious complication rate was 3.9% in the intervention group and 6.4% in the control group (RR 0.61; 95% CI 0.36-0.99; P = .049). The rates of sepsis, urinary tract infection, and fever were 0.3% vs 0.5% (P = .646), 2.3% vs 4.1% (P = .071), and 1.3% vs 1.9% (P = .443), respectively. The positive urine culture rate was 5.2% in the intervention group and 9% in the control group (RR 0.57; P = .015). There was no statistically significant difference between the groups regarding the occurrence of noninfectious adverse events. CONCLUSIONS: Intrarectal povidone-iodine cleansing plus formalin disinfection of the biopsy needle tip was associated with a reduction in infectious complications after transrectal prostate biopsy.
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Anti-Infecciosos Locais , Sepse , Infecções Urinárias , Masculino , Humanos , Povidona-Iodo/uso terapêutico , Próstata/patologia , Desinfecção , Estudos Prospectivos , Formaldeído , Biópsia/efeitos adversos , Infecções Urinárias/etiologiaAssuntos
Povidona-Iodo , Próstata , Humanos , Masculino , Povidona-Iodo/uso terapêutico , Formaldeído , Biópsia , DesinfecçãoRESUMO
BACKGROUND: The ability to metastasize is one of the most important characteristics of neoplastic cells. An imbalance between the action of some matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs drives the invasion process. Some studies have suggested that MMP-2 is involved in metastasis, while other studies have reported that collagen production by cancer cells might also contribute to motility. However, decreased expression of microRNA-29b (miR-29b), which may control MMP-2 and collagen gene expression, has been shown in prostate cancer (PCa). The objectives of the present study were to clarify whether MMP-2 as well as collagens I and III (encoded by COL1A1 and COL3A1, respectively) are controlled by miR-29b and to determine whether metastasis is altered by this relationship. METHODS: PCa DU145 and PC-3 cells were transfected with 100 µL of OPTI-MEM I containing 100 nmol of miR-29b (or its inhibitor) along with 1.5 µL of lipofectamine. Positive and negative controls were prepared using the same protocol. MMP-2, COL1A1 and COL3A1 messenger RNA (mRNA) levels were evaluated via real-time polymerase chain reaction (qRT-PCR). For qRT-PCR, 6 × 104 cells were used. Invasion studies were conducted with Matrigel assays, which simulate invasion of the extracellular matrix by neoplastic cells. After transfection of 3 × 104 cells, invasion was allowed to proceed for 48 h. Invasive cells were counted under an optical microscope. Each experiment was performed in triplicate. RESULTS: MMP-2 mRNA was not expressed in DU145 cells after transfection with miR-29b. After transfection of cells with the miR-29b inhibitor, COL1A1 (p = 0.02) and COL3A1 (p = 0.06) mRNA expression was increased in DU145 cells, and a large number of transfected DU145 and PC3 cells invaded the Matrigel membrane. CONCLUSIONS: In vitro studies showed that reducing the amount of miR-29b may lead to higher PCa cell invasion via a process that is independent of MMP-2. Collagen expression, controlled by miR-29b, may facilitate this motility process. Thus, the present study suggests that collagen production plays an active role in metastasis control and restoration of miR-29b levels may decrease metastasis. Altogether, these findings support further exploration of drug therapy targeting this aspect of the metastasis circuit.
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BACKGROUND: The imbalance between the action of the tissue inhibitors of matrix metalloproteinases (TIMPs) and the matrix metalloproteinases (MMPs) is one component of metastasis physiology. TIMP-1 overrides MMP-9 activity in cancer and might be regulated by miR-618. The aims of this study were to clarify whether TIMP-1 expression is modified by miR-618 and to clarify the effect of miR-618 expression on the invasion of prostate cancer cells. We also studied miR-618 expression in surgical specimens of patients with localized prostate cancer submitted to open radical prostatectomy. METHODS: After transfection of miR-618 or its antagonist in DU145 cells, qRT-PCR for TIMP-1/MMP-9 and both ELISA and zymography for MMP-9 were performed. Total miRNA was extracted from surgical specimens of PCa, and miR-618 expression was examined for correlations with Gleason score, pathological status and biochemical recurrence. RESULTS: DU145 cells transfected with miR-618 had a 76% reduction in TIMP-1 expression relative to control cells (p = 0.003). miR-618 inhibition reduced MMP-9 expression by 31% (p = 0.032) and MMP-9 absorbance evaluated with ELISA assay (p = 0.06).Zymography suggested higher MMP-9 activity in DU145 cells transfected with miR-618 than those transfected with miR-618 inhibitor, but the difference was not significant (p = 0.55). However, miR-618 expression was lower in surgical specimens of patients with Gleason score > 7 (p = 0.08) and more advanced disease (p = 0.07). CONCLUSIONS: In vitro, miR-618 overexpression decreases TIMP-1 and miR-618 inhibition decreases MMP-9, suggesting that miR-618 might be an oncomiR. However, the analysis of clinical samples of localized prostate cancer revealed an inconsistent pattern, as increased miR-618 expression was associated with lower Gleason score and pathological status. Further studies are needed to address whether miR-618 is a context-dependent miRNA.
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Regulação Neoplásica da Expressão Gênica , MicroRNAs/biossíntese , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Linhagem Celular Tumoral , Estudos de Coortes , Humanos , Masculino , MicroRNAs/genética , Neoplasias da Próstata/genética , Inibidor Tecidual de Metaloproteinase-1/genéticaRESUMO
OBJECTIVE: To identify factors associated with survival after palliative urinary diversion (UD) for patients with malignant ureteric obstruction (MUO) and create a risk-stratification model for treatment decisions. PATIENTS AND METHODS: We prospectively collected clinical and laboratory data for patients who underwent palliative UD by ureteric stenting or percutaneous nephrostomy (PCN) between 1 January 2009 and 1 November 2011 in two tertiary care university hospitals, with a minimum 6-month follow-up. Inclusion criteria were age >18 years and MUO confirmed by computed tomography, ultrasonography or magnetic resonance imaging. Factors related to poor prognosis were identified by Cox univariable and multivariable regression analyses, and a risk stratification model was created by Kaplan-Meier survival estimates at 1, 6 and 12 months, and log-rank tests. RESULTS: The median (range) survival was 144 (0-1084) days for the 208 patients included after UD (58 ureteric stenting, 150 PCN); 164 patients died, 44 (21.2%) during hospitalisation. Overall survival did not differ by UD type (P = 0.216). The number of events related to malignancy (≥4) and Eastern Cooperative Oncology Group (ECOG) index (≥2) were associated with short survival on multivariable analysis. These two risk factors were used to divide patients into three groups by survival type: favourable (no factors), intermediate (one factor) and unfavourable (two factors). The median survival at 1, 6, and 12 months was 94.4%, 57.3% and 44.9% in the favourable group; 78.0%, 36.3%, and 15.5% in the intermediate group; and 46.4%, 14.3%, and 7.1% in the unfavourable group (P < 0.001). CONCLUSIONS: Our stratification model may be useful to determine whether UD is indicated for patients with MUO.
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Nefrostomia Percutânea/métodos , Neoplasias Ureterais/mortalidade , Obstrução Ureteral/cirurgia , Derivação Urinária/métodos , Idoso , Brasil/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrostomia Percutânea/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Stents , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Ureterais/complicações , Neoplasias Ureterais/patologia , Obstrução Ureteral/etiologia , Obstrução Ureteral/mortalidade , Derivação Urinária/mortalidadeRESUMO
INTRODUCTION AND OBJECTIVE: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). MATERIALS AND METHODS: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. RESULTS: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. CONCLUSION: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression.
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Metaloproteinases da Matriz/análise , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Inibidor Tecidual de Metaloproteinase-1/análise , Inibidor Tecidual de Metaloproteinase-2/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Progressão da Doença , Humanos , Imuno-Histoquímica , Interleucina-8/análise , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/química , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/química , Neoplasias da Próstata/cirurgia , Estatísticas não ParamétricasRESUMO
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 ß- 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 ß- 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.
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Caderinas/metabolismo , Cateninas/metabolismo , Moléculas de Adesão Celular/metabolismo , Hipercolesterolemia/metabolismo , Miócitos de Músculo Liso/metabolismo , Obstrução do Colo da Bexiga Urinária/metabolismo , Animais , Células Cultivadas , Feminino , Miócitos de Músculo Liso/patologia , Ratos , Ratos Wistar , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Obstrução do Colo da Bexiga Urinária/patologiaRESUMO
INTRODUCTION: The knowledge about the molecular biology of clear cell renal cell carcinoma (ccRCC) is evolving, and Carbonic Anhydrase type IX (CA-IX) has emerged as a potential prognostic marker in this challenging disease. However, most of the literature about CA-IX on ccRCC comes from series on metastatic cancer, with a lack of series on non-metastatic cancer. The objective is to evaluate the expression of CA-IX in a cohort of non-metastatic ccRCC, correlating with 1) overall survival, and 2) with established prognostic parameters (T stage, tumor size, Fuhrman nuclear grade, microvascular invasion and peri-renal fat invasion). MATERIALS AND METHODS: This is a retrospective cohort study. We evaluated 95 patients with non-metastatic clear cell renal cell carcinoma, as to the expression of CA-IX. The analyzed parameters where: overall survival (OS), TNM stage, tumor size (TS), Fuhrman nuclear grade (FNG), microvascular invasion (MVI), peri-renal fat invasion (PFI). We utilized a custom built tissue microarray, and the immunoexpression was digitally quantified using the Photoshop ® software. RESULTS: The mean follow-up time was 7.9 years (range 1.9 to 19.5 years). The analysis of CA-IX expression against the selected prognostic parameters showed no correlation. The results are as follows: Overall survival (p = 0.790); T stage (p = 0.179); tumor size (p = 0.143); grouped Fuhrman nuclear grade (p = 0.598); microvascular invasion (p = 0.685), and peri-renal fat invasion (p = 0.104). CONCLUSION: Carbonic anhydrase type IX expression does not correlate with overall survival and conventional prognostic parameters in non-metastatic clear cell renal cell carcinoma.
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Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Anidrases Carbônicas/análise , Carcinoma de Células Renais/enzimologia , Neoplasias Renais/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidrase Carbônica IX , Carcinoma de Células Renais/patologia , Criança , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Fatores de Tempo , Análise Serial de Tecidos/métodos , Carga Tumoral , Adulto JovemRESUMO
UNLABELLED: Integrins are transmembrane glycoprotein receptors that regulate cell-matrix interactions, thus functioning as sensors from the environment. They also act as cell adhesion molecules that are responsible for the maintenance of the normal epithelial phenotype. Some studies have reported a correlation between carcinogenesis and changes in integrin expression, especially ß1 integrin, however its role in prostate cancer (PC) is unclear. The aim of our study was to evaluate the expression of ß1 integrin in localized PC and to correlate the pattern of expression with recurrence after surgical treatment. Methods For this case-control study, we retrospectively selected surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Recurrence was defined as a PSA level exceeding 0.2 ng/mL after surgery, and the median follow-up was 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two samples from each tumor. We employed a semiquantitative analysis and considered a case as positive when the expression was strong and diffusely present. RESULTS: There was a loss of 11 cases during the tissue micro array assembling. ß1 expression was positive in 79 of the 100 evaluated cases (79%). The univariate and multivariate analyses showed that the negative expression of ß1 integrin was associated with biochemical recurrence (p = 0.047) and time to recurrence after radical prostatectomy (p = 0.023). When ß1 was negative, the odds ratio for recurrence was 2.78 times higher than that observed in the positive cases [OR = 2.78, p = 0.047, IC 95% (1.01-7.66)]. CONCLUSIONS: The loss of ß1 integrin immune expression was correlated with biochemical recurrence in patients treated with radical prostatectomy for localized PC.
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Biomarcadores Tumorais/análise , Integrina beta1/análise , Recidiva Local de Neoplasia/química , Neoplasias da Próstata/química , Adulto , Idoso , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Fatores de TempoRESUMO
INTRODUCTION: Inguinal hernia and varicocele are common conditions in male population. Laparoscopy brings the opportunity to treat them simultaneously, through the same incision. However, there are different opinions about the risks for testicular perfusion of multiple procedures in the inguinal region. In this study, we assessed the feasibility of simultaneous laparoscopic procedures by studying clinical and surgical outcomes of patients undergoing bilateral inguinal hernioplasty using the transabdominal preperitoneal (TAPP) technique with and without concomitant bilateral laparoscopic varicocelectomy (VLB). METHODS: a sample of 20 patients from the University Hospital of USP-SP with indirect inguinal hernia and varicocele with indication for surgical correction was selected. Patients were randomized into two groups, 10 undergoing TAPP (Group I) and 10 undergoing simultaneous TAPP and VLB (Group II). Data regarding total operative time, complications and postoperative pain was gathered and analyzed. RESULTS: there was no statistical difference between groups regarding total operative time and postoperative pain. Only one complication (spermatic cord hematoma) was observed in Group I and no complications were observed in Group II. CONCLUSIONS: simultaneous TAPP and VLB in was shown to be effective and safe, which provides a basis for conducting studies on larger scales.
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Hérnia Inguinal , Laparoscopia , Varicocele , Humanos , Masculino , Hérnia Inguinal/cirurgia , Estudos de Viabilidade , Herniorrafia/métodos , Varicocele/cirurgia , Varicocele/complicações , Laparoscopia/métodos , Peritônio/cirurgia , Dor Pós-Operatória/etiologia , Telas Cirúrgicas/efeitos adversos , Resultado do Tratamento , RecidivaRESUMO
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.
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Biomarcadores Tumorais/genética , Interleucina-8/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Proteínas Ligadas por GPI/genética , Perfilação da Expressão Gênica , Humanos , Interleucina-8/genética , Masculino , Metaloproteinase 14 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Inibidores Teciduais de Metaloproteinases/genéticaRESUMO
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.
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Adenocarcinoma/metabolismo , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Neoplasias da Próstata/metabolismo , Adenocarcinoma/genética , Idoso , Biomarcadores Tumorais , Linhagem Celular Tumoral , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/genéticaRESUMO
OBJECTIVE: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). MATERIALS AND METHODS: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa. RESULTS: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). CONCLUSION: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.
Assuntos
Interleucina-8/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Adulto , Idoso , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Prostatectomia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and Α-, Β- and y-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. RESULTS: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of Α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of Α-catenin expression is related to tumor size in upper tract urothelial carcinomas.
Assuntos
Biomarcadores Tumorais/análise , Caderinas/análise , Carcinoma/química , Cateninas/análise , Neoplasias Ureterais/química , Sistema Urinário/química , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Moléculas de Adesão Celular/análise , Métodos Epidemiológicos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Distribuição por Sexo , Fatores de Tempo , Análise Serial de Tecidos , Neoplasias Ureterais/patologia , Sistema Urinário/patologia , alfa Catenina/análise , beta Catenina/análise , gama Catenina/análiseRESUMO
INTRODUCTION: retrograde intrarenal surgery (CRIR) is an evolving tool. Its learning curve is not well established, despite the common use of flexible ureteroscopes today. Our aim is to estimate the number of procedures needed for one to perform RIRS consistently. MATERIAL AND METHODS: a urology resident had his first 80 RIRS for nephrolithiasis analyzed quantitatively and qualitatively. The procedures were divided into 4 groups containing 20 surgeries each (I to IV), according to their order, for comparison. RESULTS: there was no difference in stone sizes between groups. All qualitative variables varied significantly between groups (p<0.001), except between III and IV. In the quantitative analysis, there was a difference between groups I and IV in time for double-J catheter placement (p=0.012). There was an increasing difference in sheath placement time (p<0.001) and in total operative time (p=0.004). The time fot stone treatment (p=0.011) was significant only between groups I, II and III. There was difference in total sheath time only between groups I and III (p=0.023). Stone free status did not change between groups. DISCUSSION: the differences between the qualitative and quantitative variables show the relation between number of surgeries performed and proficiency in the procedure. Intergroup comparisons show sequential optimization of parameters. CONCLUSIONS: we found that 60 is a reasonable number of surgeries to be performed in order to reach the plateau of RIRSs learning curve.
Assuntos
Cálculos Renais , Curva de Aprendizado , Humanos , Cálculos Renais/cirurgia , Duração da Cirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: semi-rigid ureteroscopy is the procedure of choice for the treatment of ureterolithiasis, but it requires a learning curve to be performed safely. OBJECTIVE: To describe an estimate of the learning curve for performing semi-rigid ureterorenolithotripsy in patients with small-sized ureterolithiasis and to estimate the minimum number of procedures necessary to safely perform the surgical procedure. METHODS: this is a prospective study evaluating the learning curve of a resident of urology in the first 60 semirigid ureteroscopies in patients with ureterolithiasis up to 1cm. The patients were divided into three groups: Group I one to twenty surgeries, Group II twenty one to forty surgeries and Group III forty one to sixty surgeries. The surgeries were recorded and analyzed by two urologists experienced in endourology. A qualitative analysis was performed based on a previously validated tool and a quantitative analysis. RESULTS: all qualitative variables had significant variation between Groups I and II (p<0.001), and between Groups I and III (p<0.001). There was a difference in time to access the ureter, passage of a double J catheter and total operative time between Groups I and II (p<0.001) and Groups I and III (p<0.001). CONCLUSION: after 40 cases there seems to be little increase in both quantitative as well as qualitative evaluation in surgical performance for performing semi-rigid ureterolithotripsy safely in calculations up to 1cm.
Assuntos
Cálculos Ureterais , Ureteroscopia , Humanos , Curva de Aprendizado , Estudos Prospectivos , Cálculos Ureterais/cirurgia , UreteroscópiosRESUMO
This study aimed to develop a valid and reliable scale for assessing food and nutritional insecurity, specifically in adolescents. The initial version of the scale consisted of two subscales: perception of food insecurity and perception of nutritional security. The items were submitted to content analysis (n = 4) by a group of food and nutrition security experts, and semantic analysis (n = 20) by a group of adolescents conveniently sampled from the target population. After adjustments, the final version of the scale was applied to adolescent students (n = 425) aged 12 to 18 years (m = 14.32±0.96; CV = 6.7%). A two-factor model was the most appropriate after performing exploratory factor analysis. The subscales showed modest values of the alpha coefficient (0.69 and 0.60, respectively). Daily consumption of fruits, vegetables and soft drinks was significantly associated with higher scores in the food and nutrition security perception scale. Therefore, it is recommended to combine food access-based items with other aspects related to attitudes and behaviors towards healthy eating in order to achieve a more accurate picture of adolescent's needs and better guide public policies.
O objetivo do trabalho foi desenvolver uma escala válida e fidedigna para a avaliação de insegurança alimentar e nutricional especificamente em adolescentes. A versão inicial da escala foi composta por duas subescalas: percepção de insegurança alimentar e percepção de segurança nutricional. Os itens elaborados foram submetidos à análise de conteúdo por peritos em segurança alimentar e nutricional (n = 4) e à análise semântica por adolescentes selecionados por conveniência e oriundos da população alvo (n=20). Após ajustes, a versão final da escala foi aplicada junto a adolescentes escolares (n = 425) com idade entre 12 e 18 anos (m = 14,32±0,96; CV = 6,7%). Após realização de análise fatorial exploratória, um modelo de dois fatores foi o que se mostrou mais adequado. As subescalas avaliadas apresentaram valores modestos do coeficiente alfa (0,69 e 0,60, respectivamente). Consumo diário de frutas, verduras e refrigerantes se mostrou significativamente associado a escores mais elevados na escala de percepção de segurança alimentar e nutricional. Sugere-se a viabilidade de combinar itens com base no acesso a alimentos com outros relacionados a atitudes e práticas de alimentação saudável de modo a obter um retrato mais aproximado das necessidades dos adolescentes e melhor orientar políticas públicas.