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Introduction/Objective. The COVID-19 pandemic affected the functioning of health care systems, including emergency services worldwide. The aim of this study was to examine the impact of the pandemic and lockdown on the care of urgent urological patients in daily practice. Methods. Data were retrospectively collected from patients urgently hospitalized at Emergency Department of Clinic of Urology, University Clinical Center of Serbia, during the first three months of lockdown between March 15 and June 15, 2020, and compared to the same period in 2019. The collected data included demographic and clinical characteristics, as well as treatment characteristics and treatment outcomes. Results. This study included 80 patients who were hospitalized during the 2020 lockdown and 68 patients who were hospitalized in the same period in 2019. There was no difference in total number of hospitalized patients, age and sex when comparing these two periods. Among patients with urinary tract infection, the number of patients with urosepsis was significantly higher in 2020 (p = 0.028). The median time from symptoms’ onset to hospitalization was significantly longer in patients who were hospitalized in 2020 (p = 0.049). No difference was found in duration of hospitalization and characteristics of treatment between the two periods. The number of deaths was significantly higher in 2020 (p = 0.034). Conclusion. During lockdown in Serbia, patients sought emergency urology service significantly later. Furthermore, a higher number of patients with urosepsis and a higher number of deaths among hospitalized patients were found during lockdown compared to the previous year.

Intravesical BCG (Bacillus Calmette–Guerin) therapy represents the therapy of choice for intermediaryand high-risk non-muscle invasive bladder cancers after transurethral resection. However, up to 40% of these patients do not show adequate response to the therapy (BCG failure) and 15% of them experience the progression of the disease to muscle-invasive bladder cancer. In such cases, radical cystectomy is indicated. Studies suggest that early radical cystectomy in patients with BCG failure is followed by better survival compared to delayed radical cystectomy. The prediction of response to BCG therapy could enable early identification of patients on which this therapy would have no effect and who should undergo early radical cystectomy.

Background/Aim. Benign prostatic hyperplasia (BPH) is a pathological process, which is one of the most common causes of so-called lower urinary tract symptoms (LUTS). LUTS affect many aspects of daily activities and almost all domains of health-related quality of life (HRQoL). The objective of this study was to evaluate the effects of operative treatment of BPH using standard clinical diagnostic procedures and effects on LUTS using the symptom-score validated to Serbian language as well as implications on HRQoL. Methods. Seventy-four patients underwent surgical treatment for BPH. The study protocol included objective and subjective parameters of the following sets of variables measured before and after the surgery: voiding and incontinence symptoms were measured using the International Continence Society male Short Form (ICS male SF) questionnaire, HRQoL was measured using the SF-36 questionnaire along with standard clinical measurement of residual urine and urine flow. Results. After the surgery, all patients had decrease of voiding scores (13.5 ± 3.3 before and 1.5 ± 1.4 after surgery) and incontinence symptoms (5.7 ± 3.9 before and 0.6 ± 0.8 after surgery) in comparison to period before operative treatment. Significant improvements in all dimensions of HRQoL were noticed, particularly in emotional health. Although mental and physical total scores were significantly better than prior to the surgery, the level of improvement of voiding and incontinence scores were significantly correlated only with the level of improvement of mental score. Conclusion. After BPH surgery, patients are likely to have normal voiding symptoms, barely some involuntary control over urination and overll better HRQoL, particularly in emotional domain.

Angiotensin-converting enzyme (ACE)-gene polymorphism is a possible predisposing factor of erythropoietin response under hypoxic conditions. However, it is not completely clear whether the ACE insertion/deletion (I/D) genotype has an impact on anemia in patients with permanent kidney failure. A 9-month prospective trial was conducted on 53 patients on hemodialysis aimed at determining the beneficial effect of oral vs intravenous iron in anemia management with recombinant human erythropoietin (rHuEpo), and identifying a possible association of the ACE gene I/D polymorphism with the response to rHuEpo. Patients were randomly allocated to receive 50-100 mg daily of ferrous gluconate orally (N=26) or intravenously every two weeks (N=27), together with rHuEpo-beta (200 IU/kg) subcutaneously, to achieve a hemoglobin increase to 105 g/L; subsequently the rHuEpo dose was adjusted at one or two week intervals. In 34 patients who regularly received ACE-inhibitor (ACEi) medication, genotyping for ACE-gene I/D polymorphism was performed using PCR, gel analysis and appropriate restriction digestion. After prolonged rHuEpo treatment, 24.5% of patients attained the targeted 9th-month hemoglobin concentration (105 g/L). Of these, 6/26 of patients received elemental iron orally and 7/27 received it intravenously. We observed an association between homozygous DD (deletion) of the ACE gene and a remarkable early increase in blood hemoglobin (p=0.028), erythrocyte count (p=0.020) and hematocrit (p=0.043) after reduction of the dose of rHuEpo (F=3.95; p=0.029), irrespective of the iron repletion mode (p=0.960). This is the first report on DD genotype as a linkage marker for the optimization of rHuEpo dose for anemia management in hemodialysis patients.

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.

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.

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.

Background: Cervical cancer is often associated with malignant ureteral obstruction and consequent hydronephrosis. Hydronephrosis caused in this way can be resolved by placing ureteral stents or performing a percutaneous nephrostomy. Complications that may occur during the retrograde ureteral stent placement are usually mild, but serious complications such as stent migration into the cardiovascular system are also possible. Here we present an unusual case where a ureteral stent entered the abdominal aorta during the cystoscopic ureteral stenting, which was resolved by a cystoscopic stent removal kept in check by endovascular catheters., Case Presentations: The 48-year-old female patient was treated in the regional secondary healthcare facility due to bilateral hydronephrosis caused by cervical cancer. The patient had bilateral percutaneous nephrostomies and ureteral stents. Due to the calcification of the left ureteral stent, an urethrorenoscopy with lithotripsy of the calculus in the left ureter was performed in the regional secondary healthcare facility, and the ureteral stent was cystoscopically replaced. The control radiography of the urinary tract showed a misplacement of the left ureteral stent, and a computed tomography showed that the stent was located in the abdominal aorta. The patient was referred to the University Clinical Center of Serbia, where a ureteral stent was cystoscopically removed from the abdominal aorta under the control of endovascular catheters. The patient was in good general condition at all times, with no signs of bleeding, and she was discharged from the hospital on the fourth postoperative day., Conclusions: The migration of a ureteral stent into the abdominal aorta and the cardiovascular system in general is a rare type of ureteral stenting complication whose treatment requires a multidisciplinary approach. In order to prevent such complications, it is necessary to strictly adhere to the indications for the ureteral stent placement in the case of malignant ureteral obstruction. Also, this procedure should be performed according to the current guidelines and controlled by an X-ray or ultrasound., (© 2022. The Author(s).)

Background and Objectives: Mounting evidence implicates oxidative damage in prostate carcinogenesis, contributing to modifications of macromolecules that drive cellular malignant transformation. Functional single-nucleotide polymorphisms (SNPs) of enzymes involved in redox homeostasis can disrupt pro-oxidant-antioxidant balance, leading to accumulation of reactive oxygen species and oxidative damage. We investigated the potential role of genetic polymorphisms of antioxidant enzymes glutathione peroxidase 1 ( GPX1 rs1050450) and superoxide dismutase 2 ( SOD2 rs4880) and regulatory antioxidant protein nuclear factor erythroid 2-related factor 2 ( Nrf2 rs6721961) in the susceptibility to prostate cancer development (PC) and prognosis. Materials and Methods: We conducted a case-control study consisting of 235 patients with PC and 240 controls. Gene polymorphisms were determined by quantitative polymerase chain reaction (qPCR) and polymerase chain reaction with confronting two-pair primers (PCR-CTTP) methods. Multiple risk models were composed to inspect the separate and mutual effect of multiple genes and in combination with acquired contributory factors on the risk of PC development. Results: Independently, carriers of at least one SOD2*C allele had increased risk of PC development, which was significantly further amplified in advanced statistical models. When tested in combination, individuals with both SOD2*C allele and Nrf2*C/C genotype were also at increased risk of PC development, which was augmented when combined with acquired contributory factors. During the mean 75 ± 25 months of follow-up, investigated gene polymorphisms did not affect overall survival. Conclusion: Our results suggest that these gene polymorphisms could be used as risk biomarkers of PC evolution.

Sustained and dysregulated inflammation, concurrent tumor-induced immune suppression, and oxidative stress are profoundly involved in cancer initiation, presentation, and perpetuation. Within this prospective study, we simultaneously analyzed the preoperative indices of systemic inflammatory response and the representative byproducts of oxidative DNA, protein, and lipid damage with the aim of evaluating their clinical relevance among patients diagnosed with testicular germ-cell tumors (GCT). In the analytical cohort (n = 88, median age 34 years), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and C-reactive protein (CRP) were significantly altered in patients with a higher tumor stage (p < 0.05). Highly suggestive correlations were found between NLR, dNLR, and SII and modified nucleoside 8-OHdG. CRP and albumin-to-globulin ratio (AGR) significantly correlated with thiols group level and maximal tumor dimension (p < 0.05). Based on receiver operating characteristic (ROC) curve analyses, all the evaluated pre-orchiectomy inflammation markers demonstrated strong performance in predicting metastatic disease; optimal cut-off points were determined for each indicator. Although further large-scale studies are warranted, inflammatory and redox indices may both complement the established tumor markers and standard clinicopathological prognostic variables and contribute to enhanced personalized risk-assessment among testicular GCT patients.

To identify the prognostic impact of tumor multifocality on upper tract urothelial carcinoma (UTUC) outcomes in patients treated with radical nephroureterectomy (RNU). Study included 342 consecutive patients with UTUC. Tumor multifocality was defined as the synchronous presence of 2 or more pathologically confirmed tumors in any upper urinary tract location. Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Tumor multifocality was significantly associated with a history of previous non-muscle invasive bladder cancer (P < 0.001), tumor size (P < 0.001), gender (P = 0.009), tumor location (P = 0.005), and anemia (P = 0.01). The Kaplan-Meier method showed that tumor multifocality was significantly associated with worse recurrence-free survival (P < 0.001, log rank). Using multivariate analysis, tumor multifocality (HR, 2.86; 95% CI, 2.06 - 3.99; P < 0.001) was independently associated with recurrence free survival. During the follow-up, a total of 128 (37.4%) patients died, including 92 (28.2%) from UTUC. However, tumor multifocality was not associated with CSS (HR, 1.29; 95% CI, 0.89 - 1.96; P = 0.21) in univariate Cox regression analyses. Tumor stage (HR, 11.1; 95% CI, 3.64 - 33.8; P < 0.001), lymph node status (HR, 2.04, 95% CI, 1.05 - 3.94; P = 0.03) and preoperative anemia (HR, 3.50, 95% CI, 2.02 - 6.08; P < 0.001) were the only independent predictors associated with worse cancer-specific survival. Tumor multifocality is an independent prognostic factor of disease recurrence in patients treated with RNU for UTUC. Tumor multifocality is unable to predict cancer specific survival in a single-center series of consecutive patients who were treated with RNU., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2021. Published by Elsevier Inc.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs' role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms ( GSTM1 , GSTT1 , and GSTP1 ). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1 *A/A and GSTO2 *G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1 *A and GSTO2 *G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms ( GSTM1 , GSTT1 , and GSTP1 ) in terms of PC prognosis has shown shorter survival in carriers of GSTP1 *T/T ( rs1138272 ) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1 *T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Santric, Dragicevic, Matic, Djokic, Pljesa-Ercegovac, Radic, Suvakov, Nikitovic, Stankovic, Milojevic, Radovanovic, Dzamic, Simic and Savic-Radojevic.)

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.

Objectives: To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder., Methods: GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls., Results: Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (P=0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (P=0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (P=0.044)., Conclusions: Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC.