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Browsing by Author "Dzamic, Zoran (6506981365)"

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    Association between GPX1 and SOD2 genetic polymorphisms and overall survival in patients with metastatic urothelial bladder cancer: a single-center study in Serbia
    (2018)
    Nikic, Predrag (55189551300)
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    Dragicevic, Dejan (6506794751)
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    Savic-Radojevic, Ana (16246037100)
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    Pljesa-Ercegovac, Marija (16644038900)
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    Coric, Vesna (55584570400)
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    Jovanovic, Djurdja (57209718540)
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    Bumbasirevic, Uros (36990205400)
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    Pekmezovic, Tatjana (7003989932)
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    Simic, Tatjana (6602094386)
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    Dzamic, Zoran (6506981365)
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    Matic, Marija (58618962300)
    Purpose: Urothelial bladder cancer (UBC) is the most common malignancy of urinary tract in the developed world. In metastatic UBC, systemic chemotherapy still remains the mainstay of initial treatment. Inter-individual differences in treatment outcome partially may be the consequence of genetic variations in enzymes that modulate oxidative stress. Therefore, we aimed to determine the potential prognostic role of single nucleotide polymorphism (SNP) of the two antioxidant enzymes glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2) in metastatic UBC patients treated with cisplatin-based chemotherapy. Methods: This prospective single-center hospital-based case-control study included 33 patients with metastatic UBC treated with cisplatin-based chemotherapy and 227 healthy controls. GPX1 SNP (rs1050450) was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SOD2 SNP (rs4880) was determined by quantitative PCR (q-PCR). Overall survival (OS) was evaluated using Kaplan–Meier survival analysis during 2-year follow up period, with the log-rank test for prognostic significance. Results: No significant difference was observed in the distributions of GPX1 and SOD2 gene variants between patients and controls (p>0.05). Regarding GPX1 polymorphism, no impact of GPX1 polymorphism on OS could be demonstrated (p>0.05). Finally, Kaplan-Meier survival analysis showed no association between SOD2 polymorphism and OS (p>0.05). Conclusions: No association was found between polymorphism of GPX1 and SOD2 and OS in patients with metastatic urothelial bladder cancer treated with cisplatin-based chemotherapy. © 2018 Zerbinis Publications. All Rights Reserved.
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    Association between GPX1 and SOD2 genetic polymorphisms and overall survival in patients with metastatic urothelial bladder cancer: a single-center study in Serbia
    (2018)
    Nikic, Predrag (55189551300)
    ;
    Dragicevic, Dejan (6506794751)
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    Savic-Radojevic, Ana (16246037100)
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    Pljesa-Ercegovac, Marija (16644038900)
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    Coric, Vesna (55584570400)
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    Jovanovic, Djurdja (57209718540)
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    Bumbasirevic, Uros (36990205400)
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    Pekmezovic, Tatjana (7003989932)
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    Simic, Tatjana (6602094386)
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    Dzamic, Zoran (6506981365)
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    Matic, Marija (58618962300)
    Purpose: Urothelial bladder cancer (UBC) is the most common malignancy of urinary tract in the developed world. In metastatic UBC, systemic chemotherapy still remains the mainstay of initial treatment. Inter-individual differences in treatment outcome partially may be the consequence of genetic variations in enzymes that modulate oxidative stress. Therefore, we aimed to determine the potential prognostic role of single nucleotide polymorphism (SNP) of the two antioxidant enzymes glutathione peroxidase 1 (GPX1) and superoxide dismutase 2 (SOD2) in metastatic UBC patients treated with cisplatin-based chemotherapy. Methods: This prospective single-center hospital-based case-control study included 33 patients with metastatic UBC treated with cisplatin-based chemotherapy and 227 healthy controls. GPX1 SNP (rs1050450) was assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and SOD2 SNP (rs4880) was determined by quantitative PCR (q-PCR). Overall survival (OS) was evaluated using Kaplan–Meier survival analysis during 2-year follow up period, with the log-rank test for prognostic significance. Results: No significant difference was observed in the distributions of GPX1 and SOD2 gene variants between patients and controls (p>0.05). Regarding GPX1 polymorphism, no impact of GPX1 polymorphism on OS could be demonstrated (p>0.05). Finally, Kaplan-Meier survival analysis showed no association between SOD2 polymorphism and OS (p>0.05). Conclusions: No association was found between polymorphism of GPX1 and SOD2 and OS in patients with metastatic urothelial bladder cancer treated with cisplatin-based chemotherapy. © 2018 Zerbinis Publications. All Rights Reserved.
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    Clinicopathological characteristics and survival in Serbian patients with renal cell carcinoma: A retrospective analysis
    (2017)
    Pavlovic, Ivan (56769363700)
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    Pejic, Snezana (6602841944)
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    Glumac, Sofija (33467624700)
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    Todorovic, Ana (8930796800)
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    Stojiljkovic, Vesna (8930796500)
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    Popovic, Natasa (15832791100)
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    Gavrilovic, Ljubica (23060209300)
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    Pajovic, Snezana B. (6701715237)
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    Radojevic-Skodric, Sanja (15726145200)
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    Dzamic, Zoran (6506981365)
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    Basta-Jovanovic, Gordana (6603093303)
    Purpose: Indications of kidney cancer outcome in lower-income countries are based on an incidence/mortality ratio due to lack of survival information. This study was conducted to provide outcome data in Serbian patients with renal cell carcinoma (RCC) and to identify prognostic factors that could affect their overall survival (OS). Methods: This retrospective study included 185 patients who underwent nephrectomy. We assessed certain clinicopathological data including age, gender, tumor size, grade, stage and histological subtypes for their possible impact on OS. Results: The 5-year OS was 63.2%. Significant association was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank 26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235, p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014) and stage (p=0.000) remained significant predictors of OS. Conclusion: Tumor grade and stage were identified as independent prognostic factors of OS survival in Serbian patients with RCC. © 2017 Zerbinis Publications. All rights reserved.
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    Clinicopathological characteristics and survival in Serbian patients with renal cell carcinoma: A retrospective analysis
    (2017)
    Pavlovic, Ivan (56769363700)
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    Pejic, Snezana (6602841944)
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    Glumac, Sofija (33467624700)
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    Todorovic, Ana (8930796800)
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    Stojiljkovic, Vesna (8930796500)
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    Popovic, Natasa (15832791100)
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    Gavrilovic, Ljubica (23060209300)
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    Pajovic, Snezana B. (6701715237)
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    Radojevic-Skodric, Sanja (15726145200)
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    Dzamic, Zoran (6506981365)
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    Basta-Jovanovic, Gordana (6603093303)
    Purpose: Indications of kidney cancer outcome in lower-income countries are based on an incidence/mortality ratio due to lack of survival information. This study was conducted to provide outcome data in Serbian patients with renal cell carcinoma (RCC) and to identify prognostic factors that could affect their overall survival (OS). Methods: This retrospective study included 185 patients who underwent nephrectomy. We assessed certain clinicopathological data including age, gender, tumor size, grade, stage and histological subtypes for their possible impact on OS. Results: The 5-year OS was 63.2%. Significant association was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank 26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235, p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014) and stage (p=0.000) remained significant predictors of OS. Conclusion: Tumor grade and stage were identified as independent prognostic factors of OS survival in Serbian patients with RCC. © 2017 Zerbinis Publications. All rights reserved.
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    Epidural anesthesia can block the negative effects of prostaglandin mediators during prostate surgery
    (2013)
    Ladjevic, Nebojsa (16233432900)
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    Durutovic, Otas (6506011266)
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    Likic-Ladjevic, Ivana (12761162800)
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    Lalic, Natasa (7003905860)
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    Mimic, Ana (55865595300)
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    Dencic, Natasa (55980896300)
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    Sreckovic, Svetlana (55979299300)
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    Dzamic, Zoran (6506981365)
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    Terzic, Milan (55519713300)
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    Vuksanovic, Aleksandar (6602999284)
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    Milenkovic-Petronic, Dragica (24923372100)
    Introduction: Inflammation plays a key role in the development of benign prostatic hyperplasia. Prostaglandin E2 (PGE2) is an important inflammation factor found in enlarged prostatic tissue that can be the main cause of inflammatory pain. The aim of this study was to investigate whether epidural anesthesia can block the negative effects of prostaglandin mediators during prostate surgery. Materials and methods: The study included 60 patients who underwent open prostatectomy. All patients were randomly allocated to one of two study groups. The first group received general anesthesia and the second group a combination of general and epidural anesthesia. Main outcome measures were plasma concentration of PGE2, adrenaline, noradrenaline, and dopamine, before induction of anesthesia and at the time of enucleation. Results: Preoperative serum concentrations of PGE2 were high in both groups. During enucleation, serum concentrations of adrenaline, noradrenaline, and dopamine increased, followed by a rise of systolic and diastolic blood pressure in the group of patients that received only general anesthesia. Serum concentration of PGE2 was at the same level as before induction of anesthesia in both groups. Conclusion: Epidural anesthesia blocks transmission of painful stimulus through the spinal cord caused by prostaglandin release and prevents the rise of catecholamines and blood pressure. Open prostatectomy can become a safer procedure performed under a combination of general and epidural anesthesia. Negative intraoperative effects of inflammatory prostate mediators during other techniques for prostate surgery could also be blocked with epidural anesthesia. © The Canadian Journal of Urology™.
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    Extraurothelial recurrence after radical nephroureterectomy: preoperative predictors and survival
    (2015)
    Dzamic, Zoran (6506981365)
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    Milojevic, Bogomir (36990126400)
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    Kajmakovic, Boris (56549005500)
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    Grozdic Milojevic, Isidora (37107616900)
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    Bojanic, Nebojsa (55398281100)
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    Sipetic Grujicic, Sandra (6701802171)
    Objective: To identify the preoperative predictors of extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). Methods: A single-center series of 238 consecutive patients who were treated with RNU for UTUC was evaluated. Recurrence-free probabilities and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards regression models were used to evaluate the association between various clinicopathological factors and EUR. Results: The median time to EUR was 17.6 months (range 3–73 months). EUR-free survival rates at 1, 3, 5, and 7 years were 87.8, 75.2, 73.5, and 72.6 %, respectively. In multivariate Cox regression analyses, tumor stage (HR 27.4; 95 % CI 7.83–95.8; p = 0.0001) and lymphovascular invasion (LVI) (HR 1.53; 95 % CI 1.22–3.12; p = 0.01) were independently associated with EUR. In patients with EUR, 5-year CSS estimate was 29.2 %. Tumor stage (HR 14.3; 95 % CI 4.55–45.2; p < 0.001) and EUR (HR 2.7; 95 % CI 1.54–4.73; p = 0.001) were the only independent predictors associated with worse CSS. Conclusions: EUR significantly affected the prognosis in patients with UTUC managed by RNU. Patient with EUR had a greater probability of having higher tumor stages, higher tumor grades, and positive LVI. Tumor stage and LVI were independently associated with a worse EUR-free survival. © 2015, Springer Science+Business Media Dordrecht.
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    GSTO1*CC genotype (Rs4925) predicts shorter survival in clear cell renal cell carcinoma male patients
    (2019)
    Radic, Tanja (35275858300)
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    Coric, Vesna (55584570400)
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    Bukumiric, Zoran (36600111200)
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    Pljesa-Ercegovac, Marija (16644038900)
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    Djukic, Tatjana (36193753800)
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    Avramovic, Natasa (23134505800)
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    Matic, Marija (58618962300)
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    Mihailovic, Smiljana (57192397265)
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    Dragicevic, Dejan (6506794751)
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    Dzamic, Zoran (6506981365)
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    Simic, Tatjana (6602094386)
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    Savic-Radojevic, Ana (16246037100)
    Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    GSTO1*CC genotype (Rs4925) predicts shorter survival in clear cell renal cell carcinoma male patients
    (2019)
    Radic, Tanja (35275858300)
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    Coric, Vesna (55584570400)
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    Bukumiric, Zoran (36600111200)
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    Pljesa-Ercegovac, Marija (16644038900)
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    Djukic, Tatjana (36193753800)
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    Avramovic, Natasa (23134505800)
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    Matic, Marija (58618962300)
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    Mihailovic, Smiljana (57192397265)
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    Dragicevic, Dejan (6506794751)
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    Dzamic, Zoran (6506981365)
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    Simic, Tatjana (6602094386)
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    Savic-Radojevic, Ana (16246037100)
    Omega class glutathione transferases, GSTO1-1 and GSTO2-2, exhibit different activities involved in regulation of inflammation, apoptosis and redox homeostasis. We investigated the the prognostic significance of GSTO1 (rs4925) and GSTO2 (rs156697 and rs2297235) polymorphisms in clear cell renal cell carcinoma (ccRCC) patients. GSTO1-1 and GSTO2-2 expression and phosphorylation status of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ /mammalian target of rapamycin (mTOR) and Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathways in non-tumor and tumor ccRCC tissue, as well as possible association of GSTO1-1 with signaling molecules were also assessed. GSTO genotyping was performed by quantitative PCR in 228 ccRCC patients, while expression and immunoprecipitation were analyzed by Western blot in 30 tissue specimens. Shorter survival in male carriers of GSTO1*C/C wild-type genotype compared to the carriers of at least one variant allele was demonstrated (p = 0.049). GSTO1*C/C genotype independently predicted higher risk of overall mortality among male ccRCC patients (p = 0.037). Increased expression of GSTO1-1 and GSTO2-2 was demonstrated in tumor compared to corresponding non-tumor tissue (p = 0.002, p = 0.007, respectively), while GSTO1 expression was correlated with interleukin-1β (IL-1β)/pro-interleukin-1β (pro-IL-1β) ratio (r = 0.260, p = 0.350). Interaction of GSTO1 with downstream effectors of investigated pathways was shown in ccRCC tumor tissue. This study demonstrated significant prognostic role of GSTO1 polymorphism in ccRCC. Up-regulated GSTO1-1 and GSTO2-2 in tumor tissue might contribute to aberrant ccRCC redox homeostasis. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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    GSTP1 RS1138272 polymorphism affects prostate cancer risk
    (2020)
    Santric, Veljko (55598984100)
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    Djokic, Milica (57215827890)
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    Suvakov, Sonja (36572404500)
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    Pljesa-Ercegovac, Marija (16644038900)
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    Nikitovic, Marina (6602665617)
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    Radic, Tanja (35275858300)
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    Acimovic, Miodrag (6508256624)
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    Stankovic, Vesna (56186752300)
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    Bumbasirevic, Uros (36990205400)
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    Milojevic, Bogomir (36990126400)
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    Babic, Uros (57189327647)
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    Dzamic, Zoran (6506981365)
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    Simic, Tatjana (6602094386)
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    Dragicevic, Dejan (6506794751)
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    Savic-Radojevic, Ana (16246037100)
    Background and Objectives: One of the most frequent genetic alterations reported to date in prostate cancer (PC) is aberrant methylation of glutathione transferase P1 (GSTP1). Taking into consideration the involvement of oxidative stress in PC pathogenesis and recent advances in scientific understanding of the role of GSTP1*Ala114Val rs1138272 polymorphism in carcinogenesis, we hypothesized that this single-nucleotide polymorphism (SNP) influences the risk of PC independently of, or in combination with, other GST polymorphisms, including GSTP1*IIe105Val rs1695 or GSTM1 and GSTT1 deletion polymorphisms. Materials and Methods: Genotyping was performed in 237 PC cases and in 236 age-matched controls by multiplex polymerase chain reaction (PCR) for deletion of GST polymorphisms and by quantitative PCR for SNPs. Results: We found that carriers of either GSTP1*Val (rs1138272) or GSTP1*Val (rs1695) variant alleles had a PC risk compared to individuals with both referent alleles (OR = 4.93, 95%CI: 2.89–8.40, p < 0.001 and OR = 1.8, 95%CI: 1.19–2.73, p = 0.006, respectively). Additionally, in a haplotype analysis we found that individuals with GSTP1*C haplotype, represented by both variant alleles (GSTP1*Val rs1695 + GSTP1*Val rs1138272), had a 5.46 times higher risk of PC development compared to individuals with the most frequent haplotype (95%CI = 2.56–11.65, p < 0.001), suggesting a potential role of those variants in PC susceptibility. A regression analysis on the number of risk-associated alleles per individual (GSTM1*active, GSTT1*null, GSTP1*Val rs1695 and GSTP1*Val rs1138272) showed a significant increase in the risk of developing PC, from 3.65-fold in carriers of two risk alleles (95%CI = 1.55–8.61, p = 0.003) to an approximately 12-fold increase in carriers of all four risk alleles (95%CI = 3.05–44.93, p < 0.001). Conclusion: Prostate cancer may be influenced by multiple glutathione transferase (GST) polymorphic genes, especially GSTP1, highlighting the role of gene–gene interactions in human susceptibility to this cancer. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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    HTERT promoter methylation and single nucleotide polymorphism (-245 T>C) affect renal cell carcinoma behavior in Serbian population
    (2018)
    Trifunovic, Jovanka (33467976000)
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    Basta-Jovanovic, Gordana (6603093303)
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    Nikolic, Nadja (55324775800)
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    Carkic, Jelena (55802211000)
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    Marjanovic, Ana (56798179100)
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    Brankovic, Marija (58122593400)
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    Radojevic-Skodric, Sanja (15726145200)
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    Prvanovic, Mirjana (57201654195)
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    Jovanovic, Aleksandar (58423375000)
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    Dzamic, Zoran (6506981365)
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    Milasin, Jelena (6603015594)
    Purpose: Renal cell carcinoma (RCC) is the most common renal cancer in adults and includes several subtypes that may be distinguished by their histology, genetic background, clinical course and responses to treatment. Human telomerase reverse transcriptase (hTERT), a crucial enzyme for telomere maintenance, has been linked to RCC development. The purpose of this study was to search for genetic and epigenetic alterations in hTERT (promoter mutations and methylation and gene amplification), and to establish a possible association between molecular and clinico-pathological characteristics of RCC. Methods: DNA was extracted from 31 formalin-fixed, paraffin-embedded tumor samples and 23 blood samples from 54 patients with RCC. Polymerase chain reaction (PCR) products were sequenced and analyzed using the Sequencher software. HTERT amplification was determined by quantitative PCR, while the promoter methylation status was assessed by methylation specific PCR. Statistical analysis was performed using SPSS. Results: No mutations could be detected in the hTERT promoter but only a single nucleotide polymorphism (SNP) (-245 T>C). In 54 analyzed RCC cases, the variant allele C was present in homozygous or heterozygous form in 48% of the patients. The C allele was significantly more frequent in low grade tumors (p=0.046). Gene amplification was detected in 19.4% of the 31 RCCs and hTERT methylation in 54.8% of the 31 samples. An association was established between methylation and histological type of RCC (p=0.047). Conclusions: HTERT seems to be implicated in RCC pathogenesis since the promoter polymorphism exerts a modulation effect on tumor behavior. In addition, hTERT promoter methylation status is related to RCC histology. © 2018 Zerbinis Publications. All Rights Reserved.
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    HTERT promoter methylation and single nucleotide polymorphism (-245 T>C) affect renal cell carcinoma behavior in Serbian population
    (2018)
    Trifunovic, Jovanka (33467976000)
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    Basta-Jovanovic, Gordana (6603093303)
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    Nikolic, Nadja (55324775800)
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    Carkic, Jelena (55802211000)
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    Marjanovic, Ana (56798179100)
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    Brankovic, Marija (58122593400)
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    Radojevic-Skodric, Sanja (15726145200)
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    Prvanovic, Mirjana (57201654195)
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    Jovanovic, Aleksandar (58423375000)
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    Dzamic, Zoran (6506981365)
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    Milasin, Jelena (6603015594)
    Purpose: Renal cell carcinoma (RCC) is the most common renal cancer in adults and includes several subtypes that may be distinguished by their histology, genetic background, clinical course and responses to treatment. Human telomerase reverse transcriptase (hTERT), a crucial enzyme for telomere maintenance, has been linked to RCC development. The purpose of this study was to search for genetic and epigenetic alterations in hTERT (promoter mutations and methylation and gene amplification), and to establish a possible association between molecular and clinico-pathological characteristics of RCC. Methods: DNA was extracted from 31 formalin-fixed, paraffin-embedded tumor samples and 23 blood samples from 54 patients with RCC. Polymerase chain reaction (PCR) products were sequenced and analyzed using the Sequencher software. HTERT amplification was determined by quantitative PCR, while the promoter methylation status was assessed by methylation specific PCR. Statistical analysis was performed using SPSS. Results: No mutations could be detected in the hTERT promoter but only a single nucleotide polymorphism (SNP) (-245 T>C). In 54 analyzed RCC cases, the variant allele C was present in homozygous or heterozygous form in 48% of the patients. The C allele was significantly more frequent in low grade tumors (p=0.046). Gene amplification was detected in 19.4% of the 31 RCCs and hTERT methylation in 54.8% of the 31 samples. An association was established between methylation and histological type of RCC (p=0.047). Conclusions: HTERT seems to be implicated in RCC pathogenesis since the promoter polymorphism exerts a modulation effect on tumor behavior. In addition, hTERT promoter methylation status is related to RCC histology. © 2018 Zerbinis Publications. All Rights Reserved.
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    Immunohistochemical expression of proliferative markers in renal cell carcinoma
    (2018)
    Trifunovic, Jovanka (33467976000)
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    Prvanovic, Mirjana (57201654195)
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    Jovanovic, Aleksandar (58423375000)
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    Dzamic, Zoran (6506981365)
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    Lazic, Miodrag (35929198300)
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    Ristanovic, Momcilo (56357953700)
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    Radojevic-Skodric, Sanja (15726145200)
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    Basta-Jovanovic, Gordana (6603093303)
    Purpose: The purpose of this study was to investigate into the expression of cyclin A and telomerase in renal cell carcinoma (RCC) and to analyze the relationship between expression and the clinicopathological characteristics of the tumor and their impact on survival. Methods: The overall material included 74 samples of RCC and 4 of normal renal tissue. Primary cyclin A antibody from Santa Cruz Biotechnology and TERT MA5-16034 antibody from Thermo Fisher Scientific Inc were used. Staining was performed by streptavidin-biotin technique using DAKO LSAB+ kit. Statistical analyses were performed using of SPSS 23 Statistics software from IBM. Results: No differences in cyclin A and telomerase expression among gender and age groups were found, nor did the tumor dimensions have any significant impact on expression. Also, tumor grades and stages did not differ. However, histological types differed in favor of the papillary type. A significant positive correlation between both markers, as well as between the expression and tumor stage and grade was noticed. Only the tumor stage had negative impact on survival. Conclusions: Although not affecting survival, the expression of cyclin A and telomerase increased with tumor stage and grade, suggesting that cyclin A and telomerase could be potential proliferative immunohistochemical markers of RCC. © 2018 Zerbinis Publications. All Rights Reserved.
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    Immunohistochemical expression of proliferative markers in renal cell carcinoma
    (2018)
    Trifunovic, Jovanka (33467976000)
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    Prvanovic, Mirjana (57201654195)
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    Jovanovic, Aleksandar (58423375000)
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    Dzamic, Zoran (6506981365)
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    Lazic, Miodrag (35929198300)
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    Ristanovic, Momcilo (56357953700)
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    Radojevic-Skodric, Sanja (15726145200)
    ;
    Basta-Jovanovic, Gordana (6603093303)
    Purpose: The purpose of this study was to investigate into the expression of cyclin A and telomerase in renal cell carcinoma (RCC) and to analyze the relationship between expression and the clinicopathological characteristics of the tumor and their impact on survival. Methods: The overall material included 74 samples of RCC and 4 of normal renal tissue. Primary cyclin A antibody from Santa Cruz Biotechnology and TERT MA5-16034 antibody from Thermo Fisher Scientific Inc were used. Staining was performed by streptavidin-biotin technique using DAKO LSAB+ kit. Statistical analyses were performed using of SPSS 23 Statistics software from IBM. Results: No differences in cyclin A and telomerase expression among gender and age groups were found, nor did the tumor dimensions have any significant impact on expression. Also, tumor grades and stages did not differ. However, histological types differed in favor of the papillary type. A significant positive correlation between both markers, as well as between the expression and tumor stage and grade was noticed. Only the tumor stage had negative impact on survival. Conclusions: Although not affecting survival, the expression of cyclin A and telomerase increased with tumor stage and grade, suggesting that cyclin A and telomerase could be potential proliferative immunohistochemical markers of RCC. © 2018 Zerbinis Publications. All Rights Reserved.
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    Immunohistochemical study of cyclin A and p16 expression in patients with renal cell carcinoma
    (2017)
    Latic, Dragana (57201659994)
    ;
    Radojevic-Skodric, Sanja (15726145200)
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    Nikolic, Srdjan (56427656200)
    ;
    Prvanovic, Mirjana (57201654195)
    ;
    Lazic, Miodrag (35929198300)
    ;
    Dzamic, Zoran (6506981365)
    ;
    Bogdanovic, Ljiljana (24167847400)
    ;
    Radunovic, Milena (56490840800)
    ;
    Vukovic, Marina (57213381743)
    Purpose: Renal cell carcinoma (RCC) is the most common malignant kidney tumor in adults. Dysregulation of the cell cycle can lead to cancer development. In this study, the mitosis-associated cyclin A and p16, a negative controller, were investigated as potential key points in the RCC development. Methods: This retrospective study included 74 patients with RCC. The expression of cyclin A and p16 and their correlation to histopathological parameters (TNM stage, histological subtype, nuclear grade, tumor size), gender, age, and clinical outcome were studied and analyzed. Results: The highest median value for cyclin A (40%; range 0-70)) and for p16 (57.5%; range 35-80) were found in the papillary histological subtype. Survival analysis showed that in the group of patients that had died before September 2015, the median value for cyclin A was 20% (range 0-60), which was significantly higher than 5% (range 0-70), found in the group of patients that survived (p=0.019). Conclusions: In relation to the histological subtype, the papillary type of RCC was associated with a significantly higher expression of cyclin A and p16 compared to other subtypes of RCC. High expression of cyclin A indicated worse prognosis, therefore cyclin A could be considered to be a significant prognostic marker. © 2017 Zerbinis Publications. All rights reserved.
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    Immunohistochemical study of cyclin A and p16 expression in patients with renal cell carcinoma
    (2017)
    Latic, Dragana (57201659994)
    ;
    Radojevic-Skodric, Sanja (15726145200)
    ;
    Nikolic, Srdjan (56427656200)
    ;
    Prvanovic, Mirjana (57201654195)
    ;
    Lazic, Miodrag (35929198300)
    ;
    Dzamic, Zoran (6506981365)
    ;
    Bogdanovic, Ljiljana (24167847400)
    ;
    Radunovic, Milena (56490840800)
    ;
    Vukovic, Marina (57213381743)
    Purpose: Renal cell carcinoma (RCC) is the most common malignant kidney tumor in adults. Dysregulation of the cell cycle can lead to cancer development. In this study, the mitosis-associated cyclin A and p16, a negative controller, were investigated as potential key points in the RCC development. Methods: This retrospective study included 74 patients with RCC. The expression of cyclin A and p16 and their correlation to histopathological parameters (TNM stage, histological subtype, nuclear grade, tumor size), gender, age, and clinical outcome were studied and analyzed. Results: The highest median value for cyclin A (40%; range 0-70)) and for p16 (57.5%; range 35-80) were found in the papillary histological subtype. Survival analysis showed that in the group of patients that had died before September 2015, the median value for cyclin A was 20% (range 0-60), which was significantly higher than 5% (range 0-70), found in the group of patients that survived (p=0.019). Conclusions: In relation to the histological subtype, the papillary type of RCC was associated with a significantly higher expression of cyclin A and p16 compared to other subtypes of RCC. High expression of cyclin A indicated worse prognosis, therefore cyclin A could be considered to be a significant prognostic marker. © 2017 Zerbinis Publications. All rights reserved.
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    Partial versus radical nephrectomy for pT1a renal cancer in Serbia
    (2016)
    Janicic, Aleksandar (6505922639)
    ;
    Bumbasirevic, Uros (36990205400)
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    Pekomezovic, Tatjana (57193536421)
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    Cekerevac, Milica (18433619600)
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    Acimovic, Miodrag (6508256624)
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    Dzamic, Zoran (6506981365)
    ;
    Tulic, Cane (6602213245)
    Purpose: To assess the treatment outcome ofpTla renal tumors, comparing overall survival (OS) in patients treated with radical nephrectomy (RN) and partial nephrectomy (PN), and to examine the rate of utilization of PN in a tertiary institution in Serbia. Methods: Included were patients treated for pTla kidney tumors with open RN or open PN during 1996-2013. The inclusion criterion was the pathological tumor stage Tla. Exclusion criteria were higher pathological stages, metastatic presentation, or imperative indications for partial nephrectomy. Patients werefollowed-up every 3 to 4 months for the first year after surgery, every 6 months until the 5th year, and annually thereafter. Results: 286 patients were included in the study, and PN was performed in 177 (61.9%) of them, whereas RN was performed in the remaining 109 (38.1%). The median follow-up for the entire group was 42.0 months (interquartile range 74.5). There were no statistically significant differences between groups in cancer-specific survival (CSS) (log-rank=0.506; p=0.477). Patients selected for RN were more likely to be older, symptomatic at presentation, and have larger tumors. There was no statistically significant difference in OS between the two groups (log-rank=2.616; p=0.106). In 1996, 20% of the patients were treated with PN; this number increased to 88% in 2013. Conclusion: We did not find OS advantage for PN compared to RN in the setting of a developing country. The use of PN is increasing and is now utilized for -90% ofpTla renal tumors.
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    Partial versus radical nephrectomy for pT1a renal cancer in Serbia
    (2016)
    Janicic, Aleksandar (6505922639)
    ;
    Bumbasirevic, Uros (36990205400)
    ;
    Pekomezovic, Tatjana (57193536421)
    ;
    Cekerevac, Milica (18433619600)
    ;
    Acimovic, Miodrag (6508256624)
    ;
    Dzamic, Zoran (6506981365)
    ;
    Tulic, Cane (6602213245)
    Purpose: To assess the treatment outcome ofpTla renal tumors, comparing overall survival (OS) in patients treated with radical nephrectomy (RN) and partial nephrectomy (PN), and to examine the rate of utilization of PN in a tertiary institution in Serbia. Methods: Included were patients treated for pTla kidney tumors with open RN or open PN during 1996-2013. The inclusion criterion was the pathological tumor stage Tla. Exclusion criteria were higher pathological stages, metastatic presentation, or imperative indications for partial nephrectomy. Patients werefollowed-up every 3 to 4 months for the first year after surgery, every 6 months until the 5th year, and annually thereafter. Results: 286 patients were included in the study, and PN was performed in 177 (61.9%) of them, whereas RN was performed in the remaining 109 (38.1%). The median follow-up for the entire group was 42.0 months (interquartile range 74.5). There were no statistically significant differences between groups in cancer-specific survival (CSS) (log-rank=0.506; p=0.477). Patients selected for RN were more likely to be older, symptomatic at presentation, and have larger tumors. There was no statistically significant difference in OS between the two groups (log-rank=2.616; p=0.106). In 1996, 20% of the patients were treated with PN; this number increased to 88% in 2013. Conclusion: We did not find OS advantage for PN compared to RN in the setting of a developing country. The use of PN is increasing and is now utilized for -90% ofpTla renal tumors.
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    Primary dorsal buccal mucosa graft urethroplasty for anterior urethral strictures in patients with lichen sclerosus
    (2016)
    Acimovic, Miodrag (6508256624)
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    Milojevic, Bogomir (36990126400)
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    Milosavljevic, Marko (57052454400)
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    Skrodzka, Marta (21934918700)
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    Radovanovic, Milan (35280696600)
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    Rafailovic, Dragutin (56016907300)
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    Dzamic, Zoran (6506981365)
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    Djokic, Jovan Hadzi (54880695300)
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    Djinovic, Rados (20734254600)
    Purpose: To report our ongoing experience with dorsal buccal mucosa graft (BMG) urethroplasty for the primary repair of anterior urethral strictures in patients with lichen sclerosus (LS). Patients and methods: A total of 32 men with LS underwent BMG urethroplasty from January 2010 to September 2012. In 27 patients, stricture was limited to the penile urethra, while in five patients, both bulbar and penile urethra were involved. In these five patients, the entire anterior urethra was replaced with BMG. In nine (28.1 %) younger patients (mean age 38.2 years, range 33–45), with adverse local conditions and significant scarring, two-stage repair was done. The paired t test was performed on preoperative and postoperative Qmax as well as on preoperative and postoperative post-void residual urine volume, and the Fisher exact test was used to assess success between treatment groups. The chi-squared test was used to compare categorical data. Results: The overall success rate was 90.6 %. Complications occurred in 9.4 % of the patients (3 of 32) including hematoma in two patients and fistula in one patient. In this cohort of patients, mean preoperative Qmax was 6.2 ml per second (range 2.6–10.2) versus 18.2 (range 15.8–21.2) postoperatively (at 9 months), which was statistically significant (p < 0.002). Also, mean preoperative post-void residual urine volume was 110 ml (range 75–180) versus 19 ml (range 10–40) postoperatively at 9 months, which was statistically significant (p < 0.004). Conclusion: Buccal mucosa is the most reliable graft for repairing anterior urethral strictures in patients with LS. Minimal complications are observed, even in cases of long stenosis completely afflicting anterior urethra. © 2016, Springer Science+Business Media Dordrecht.
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    Prognostic Impact of Preoperative Anemia on Urothelial and Extraurothelial Recurrence in Patients with Upper Tract Urothelial Carcinoma
    (2015)
    Milojevic, Bogomir (36990126400)
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    Dzamic, Zoran (6506981365)
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    Kajmakovic, Boris (56549005500)
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    Durutovic, Otas (6506011266)
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    Bumbasirevic, Uros (36990205400)
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    Sipetic Grujicic, Sandra (6701802171)
    Background: To investigate the prognostic impact of preoperative anemia on urothelial and extraurothelial recurrence after radical nephroureterectomy. Methods: A single-center series of 238 consecutive patients who were treated with radical nephroureterectomy for upper tract urothelial carcinoma was evaluated. We categorized patients on the basis of hemoglobin level into 2 groups, including normal or anemia. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to evaluate the association of preoperative anemia with outcome, controlling for clinicopathologic variables. Results: Ninety-seven patients (40.8%) had anemia (median hemoglobin level, 143 vs. 107 g/L). Preoperative anemia was associated with history of bladder cancer (P =.01), tumor multifocality (P =.03), lymphovascular invasion (P =.05), and adjuvant chemotherapy (P =.01). Higher tumor stage and grade, and lymph node metastasis were significantly associated with preoperative anemia. Preoperative anemia was independently associated with extraurothelial recurrence (hazard ratio, 1.95; 95% confidence interval, 1.14-3.34; P =.01) in multivariate Cox regression analyses. Only a history of bladder tumor (hazard ratio, 2.07; P =.009) and tumor multifocality (hazard ratio, 3.97; 95% confidence interval, 2.37-6.67; P <.001) were independently associated with urothelial recurrence. The 5-year cancer-specific survival for patients with normal hemoglobin level was 82.1% and for patients with preoperative anemia was 54.2%. Conclusion: Patients with preoperative anemia had a greater probability of having upper tract urothelial carcinoma with higher tumor stages, higher tumor grades, and lymph node metastasis (pN+). Preoperative anemia was statistically significantly associated with worse cancer-specific survival and extraurothelial recurrence in patients who underwent radical nephroureterectomy. © 2015 Elsevier Inc. All rights reserved.
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    Prognostic value of Balkan endemic nephropathy and gender on upper tract urothelial carcinoma outcomes after radical nephroureterectomy: A cohort study
    (2021)
    Milojevic, Bogomir (36990126400)
    ;
    Dzamic, Zoran (6506981365)
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    Grozdic Milojevic, Isidora (37107616900)
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    Bumbasirevic, Uros (36990205400)
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    Santric, Veljko (55598984100)
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    Kajmakovic, Boris (56549005500)
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    Janicic, Aleksandar (6505922639)
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    Durutovic, Otas (6506011266)
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    Dragicevic, Dejan (6506794751)
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    Bojanic, Nebojsa (55398281100)
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    Radisavcevic, Djordje (57222992997)
    ;
    Sipetic Grujicic, Sandra (6701802171)
    Background: To identify the prognostic impact of residence in a BEN-endemic area and gender on upper tract urothelial carcinoma (UTUC) outcomes in Serbian patients treated with radical nephroureterectomy (RNU). Methods: The study included 334 consecutive patients with UTUC. Patients with permanent residence in Balkan endemic nephropathy (BEN) or non-endemic areas from their birth to the end of follow-up were included in the analysis. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Results: Female patients were more likely to have preoperative pyuria (P = 0.01), tumor multifocality was significantly associated with the female gender (P = 0.003). Gender was not associated with pathologic stage and grade, lymph node metastasis, lymphovascular invasion, adjuvant chemotherapy, bladder cancer history, tumor size, distribution of tumor location, preoperative anemia and demographic characteristics. A total of 107 cases recurred, with a median time to bladder recurrence of 24.5 months. History of bladder tumor (HR, 1.98; P = 0.005), tumor multifocality (HR, 3.80; P < 0.001) and residence in a BEN-endemic area (HR, 1.81; P = 0.01) were independently associated with bladder cancer recurrence. The 5-year bladder cancer RFS for the patients from areas of BEN was 77.8 % and for the patients from non-BEN areas was 64.7 %. The 5-year CSS for the men was 66.2% when compared to 66.6% for the women (P = 0.55). Conclusions: Residence in a BEN-endemic area represents an independent predictor of bladder cancer recurrence in patients who underwent RNU. Gender cannot be used to predict outcomes in a single-centre series of consecutive patients who were treated with RNU for UTUC. © 2021 Elsevier Inc.
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