Browsing by Author "Nikic, Predrag (55189551300)"

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.

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.

Background and Objectives: Radical prostatectomy (RP) stands as the predominant instigator of postoperative stress urinary incontinence. Techniques such as the preservation of the neurovascular bundles, bladder neck preservation, and ensuring longer postoperative urethral length have shown positive impacts on continence. The posterior reconstruction is another method that aids in early continence recovery. Anterior suspension as simulator of puboprostatic ligaments is another factor. Materials and Methods: This study was conducted in the Clinic of Urology, University Clinical Center of Serbia, between December 2014 and January 2020, employing a prospective, non-randomized comparative design. Data were meticulously gathered from 192 consecutive patients. The process of regaining continence was monitored at intervals of 1, 3, 6, 12, and 24 months after surgery. The main criterion for assessing the level of urinary continence was the number of pads used daily. Results: The distribution of overall continence rates in the BNP vs. no-BNP group at 3, 6 and 12 months was 86% vs. 60% (p < 0.0001), 89% vs. 67% (p < 0.0001), 93% vs. 83% (p = 0.022). Continence rates in non-posterior reconstruction group (10%, 22%, 34%, and 54% at 1, 3, 6, and 12 months) were statistically significantly lower (p < 0.0001). The patients who underwent urethral suspension exhibited significantly higher rates of overall continence at 1 mo (73% vs. 29%, p < 0.0001), 3 mo (85% vs. 53%, p < 0.001), 6 mo (89% vs. 62%, p < 0.0001), 12 mo (95% vs. 76%, p < 0.0001), and 24 mo (93% vs. 81%, p = 0.007). Patients who underwent urethral suspension had a four-fold greater likelihood of regaining continence (p = 0.015). Conclusions: Patients who underwent urethral suspension or BNP or posterior reconstruction had higher continence rates. Only the urethral suspension was found to be a significant prognostic factor of continence recovery. © 2024 by the authors.

Background and Objectives: Oxidative stress induced by increased reactive oxygen species (ROS) production plays an important role in carcinogenesis. The entire urinary tract is continuously exposed to numerous potentially mutagenic environmental agents which generate ROS during their biotransformation. In first line defense against free radicals, antioxidant enzymes superoxide dismutase (SOD2) and glutathione peroxidase (GPX1) both have essential roles. Altered enzyme activity and decreased ability of neutralizing free oxygen radicals as a consequence of genetic polymorphisms in genes encoding these two enzymes are well described so far. This study aimed to investigate the association of GPX1 (rs1050450) and SOD2 (rs4880) genetic variants with the urothelial bladder cancer (UBC) risk independently and in combination with smoking. Furthermore, we aimed to determine whether the UBC stage and pathological grade were influenced by GPX1 and SOD2 polymorphisms. Material and Methods: The study population included 330 patients with UBC (mean age 65 ± 10.3 years) and 227 respective controls (mean age 63.4 ± 7.9 years). Single nucleotide polymorphism (SNP) of GPX1 (rs1050450) was analyzed using the PCR-RFLP, while SOD2 (rs4880) SNP was analyzed using the q-PCR method. Results: Our results showed that UBC risk was significantly increased among carriers of at least one variant SOD2 Val allele compared to the SOD2 Ala16Ala homozygotes (OR = 1.55, p = 0.03). Moreover, this risk was even more pronounced in smokers with at least one variant SOD2 Val allele, since they have even 7.5 fold higher UBC risk (OR = 7.5, p < 0.001). Considering GPX1 polymorphism, we have not found an association with UBC risk. However, GPX1 genotypes distribution differed significantly according to the tumor stage (p ˂ 0.049) and pathohistological grade (p ˂ 0.018). Conclusion: We found that SOD2 genetic polymorphism is associated with the risk of UBC development independently and in combination with cigarette smoking. Furthermore, we showed that GPX1 genetic polymorphism is associated with the aggressiveness of the disease. © 2023 by the authors.

In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients. © 2023 by the authors.

Objective: To evaluate the prognostic factors for survival and disease recurrence in patients treated surgically for upper tract urothelial carcinoma (UTUC), focusing especially on the impact of history of non-muscle-invasive bladder cancer. Patients and methods: A single-center series of 221 consecutive patients who were treated surgically for UTUC between January 1999 and December 2010 was evaluated. Patients who had a history of bladder tumor at a higher stage than the upper tract disease, preoperative chemotherapy, or previous contralateral UTUC were excluded. None of the patients included in this study had distant metastasis at diagnosis of UTUC. In total, 183 patients (mean age 66 years, range 36-88) were then available for evaluation. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location (renal pelvis or ureter). All patients were treated with either open radical nephroureterectomy (RNU) or open conservative surgery. Recurrence-free probabilities and cancer-specific survival were estimated using the Kaplan-Meier method and Cox regression analyses. Results: Fifty-one patients (28%) had previous carcinoma not invading bladder muscle. Previous history of non-muscle-invasive bladder cancer was significantly associated with tumor multifocality (P < 0.001), concomitant bladder cancer (P < 0.001), higher tumor stage (P = 0.020), and lymphovascular invasion (P = 0.026). Using univariate analyses, history of non-muscle-invasive bladder cancer was significantly associated with an increased risk of both any recurrence (HR = 2.17; P = 0.003) and bladder-only recurrence (HR = 3.17; P = 0.001). Previous carcinoma not invading bladder muscle (HR = 2.58; P = 0.042) was an independent predictor of bladder-only recurrence. Overall 5-year disease recurrence-free (any recurrence and bladder-only recurrence) survival rates were 66.7% and 77%, respectively. Previous history of non-muscle-invasive bladder cancer was not associated with cancer-specific survival. Our results are subject to the inherent biases associated with high-volume tertiary care centers. Conclusions: Patients with previous history of non-muscle-invasive bladder cancer had a higher risk of having multifocal and UTUC with higher tumor stages (pT3 or greater). History of bladder tumor was an independent predictor of bladder cancer recurrence but had no effect on non-bladder recurrence, and cancer-specific survival in patients who underwent surgical treatment of UTUC. © 2013 Elsevier Inc.

To compare the total fluoroscopy time (FT) based on the fluoroscopy mode used—continuous vs. pulsed—in patients who underwent percutaneous nephrolithotomy (PCNL). The study cohort evaluated 111 patients who underwent PCNL by a single surgeon. Standard (continuous) fluoroscopy of 30 frames per second (fps) was used in the first 56 cases (SF group), while the next 55 consecutive cases were performed under pulsed fluoroscopy of two fps (PF group). The presence of surgeon’s previous experience decreased the possible impact of the learning curve on the outcome. In both groups, using ultrasound in combination to fluoroscopy performed the renal access. The stone complexity was determined using Guy’s stone score (GSS). Complications were evaluated using Clavien-Dindo classification. Median FT was significantly lower in PF group (76.8 s) compared to SF group (155.4 s) (p < 0.001). Stone-free rate was related to the Guy’s stone score (GSS) classification reaching 100 % in GSS 1 cases in both groups. In GSS 2 cases the stone free rate was 87.5 % in SF group, while in PF group it was 92.3 %. Stone free rate in GSS 3 cases was 73.3 and 85.7 % in SF and PF groups, respectively. In cases of GSS 4 stone free rate was 52 % in SF group and 55.6 % in PF group, respectively. Presence of residual fragments and complications were comparable in both groups. Following ultrasound-guided puncture during PCNL, the use of pulsed fluoroscopy leads to significantly lower radiation exposure comparing to the use of continuous fluoroscopy. This advantage does not compromise the safety and efficacy of the procedure. © 2016, Springer-Verlag Berlin Heidelberg.

Background: The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available. Methods: This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date. Results: The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4). Conclusions: With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC. Copyright © 2022 Nikic, Babovic, Dzamic, Salma, Stojanovic, Matkovic, Pejcic, Juskic and Soldatovic.

Background: The emerging new standard of care for metastatic clear cell renal carcinoma (mRCC) becomes a challenge when access to new drugs is limited. In Serbia, sunitinib and pazopanib are the only available first-line therapies. The second-line treatment for mRCC has never been and is still not available. We aimed to assess overall survival (OS) in patients with mRCC who received first-line sunitinib or pazopanib when access to second-line treatment was not available. Methods: This retrospective observational study analyzed data from a nationally representative cohort of 759 patients who started on first-line sunitinib or pazopanib between 1 January 2012 and 30 June 2019, in 4 centers in Serbia. The data cut-off date was 31 December 2019. Key eligibility criteria were clear cell RCC histology, measurable metastatic disease, performance status 0 or 1, and the Memorial Sloan Kettering Cancer Center favorable or intermediate prognosis. The primary outcome was OS from the start of first-line treatment to death or data cut-off date. Results: The study population included 759 patients with mRCC who started with first-line sunitinib (n = 673; [88.7%]) or pazopanib (n = 86; [11.3%]). Overall, the mean age was 61.0 ± 9.7 years at treatment baseline, and 547 (72%) were men. mRCC was primarily diagnosed in 230 (30%) patients, and most of them underwent cytoreductive nephrectomy prior to systemic therapy (n = 181 [79%]). Additional treatment of metastases prior to and/or during treatment was used in 169 patients (22.3%). Grade 3 and 4 adverse events occurred in 168 (22.1%) and 47 patients (6.2%), respectively, and treatment was permanently stopped because of toxicity in 41 (6.9%). The OS was calculated from the start of first-line treatment, and the median follow-up was 14 months (range, 0–97). The median OS in the entire cohort was 17 months (95% CI, 14.6–19.4). Conclusions: With only available sunitinib and pazopanib in first-line treatment, modest improvements are seen in the overall survival of patients with mRCC in real world clinical practice. In circumstances of limited availability of cancer medicines, our results can contribute to accelerating patient access to novel cancer therapies that have been shown to prolong survival in mRCC. Copyright © 2022 Nikic, Babovic, Dzamic, Salma, Stojanovic, Matkovic, Pejcic, Juskic and Soldatovic.

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients’ attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients’ sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor’s advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients’ sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients. © 2023 by the authors.

At the time when mass COVID-19 vaccination began, providing appropriate vaccination advice to uro-oncology patients became a challenge. This was a single-center cross-sectional observational study aimed to investigate the rate of COVID-19 vaccination among uro-oncology patients receiving systemic therapy for metastatic renal cell carcinoma and metastatic castration-resistant prostate cancer. Furthermore, we aimed to assess patients’ attitudes and identify factors influencing their decision to vaccinate against COVID-19. Data on patients’ sociodemographic characteristics, vaccination status, and awareness and attitudes about COVID-19 vaccination were collected from questionnaires completed by the patients. A total of 173 patients were enrolled in this study, and 124 (71.7%) of them completed the COVID-19 vaccination. Significantly higher vaccination rates were found in male patients, and also in older patients, highly educated patients, and those who lived with one household member. Furthermore, we found significantly higher vaccination rates in patients who had consulted with doctors involved in their treatment, particularly with urologists. A significant association was observed between COVID-19 vaccination and doctor’s advice, family member influence, and personal beliefs toward the vaccination. Our study showed multiple associations of patients’ sociodemographic characteristics with vaccination rates. Furthermore, consultation with doctors who are particularly involved in oncology treatment and advice received from them were associated with significantly higher vaccination rates among uro-oncology patients. © 2023 by the authors.

Background and Objective: To assess the oncologic and functional outcomes of testicular sparing surgery (TSS) based on a single institution experience. Methods: Forty-one patients with bilateral and 3 patients with solitary testicle tumors were referred to our institution. The inclusion criteria for TSS were normal serum testosterone levels, and tumor size (<2 cm). Sperm analysis and hormone status evaluation were performed preoperatively and postoperatively. None of the patients underwent local radiation therapy following TSS for reasons of fertility preservation. Results: A total of 26 TSS were performed in 24 patients. The median follow-up period was 51.0 months. Seven patients developed local recurrence, of which 5 had TIN and were subjected to radical orchiectomy, whereas re-do TSS was done in remaining 2 patients. The overall survival of the study group was 100%, and the presence of testicular intraepithelial neoplasia (TIN) was associated with worse recurrence-free survival (P = 0.031, log-rank). Testosterone values were normal in all of the patients, while 4 patients achieved conception. Conclusions: TSS is acceptable from an oncological point of view, and it enables continuation of a patient's life without lifelong hormonal substitution. Additionally, local irradiation therapy could be delayed in patients with TIN who wish to father children, but with high local recurrence rate. © 2014 Wiley Periodicals, Inc.

Considering the divergent biological behaviors of certain histological subtypes of urothelial carcinoma, it would be of great importance to examine the impact of variant histology and to predict its presence in patients with bladder cancer. A single-center cohort study included 459 patients who underwent radical cystectomy for urothelial carcinoma between 2017 and 2021. Patients were followed up with until July 2022. We compared clinical, laboratory, and histopathologic characteristics and the overall survival between patients with pure urothelial carcinoma and variant histologies. Our results showed that the patients with variant histology were older and preoperatively more frequently had hydronephrosis and higher values of leukocytes and neutrophils. Also, we found a significant association between variant histology and an advanced stage of tumor disease, the presence of lymphovascular invasion, positive surgical margins, and metastases in surgically resected lymph nodes. The number of neutrophils was identified as an independent preoperative predictor of the presence of variant histology after a radical cystectomy. The overall survival of the patients with variant histology was significantly lower compared to the patients with pure urothelial carcinoma. According to our results, the presence of variant histology represents a more aggressive form of the disease. Preoperative neutrophil counts may indicate the presence of variant histology of urothelial carcinoma in patients with bladder cancer. © 2023 by the authors.