Primary embryonal carcinoma of the prostate.

Extragonadal germ cell tumors originating in the prostate are extremely rare. Thus far, less than 20 cases were described in the literature. To our knowledge, there are no published cases of primary embryonal carcinoma of the prostate. The present study presents a case of a 24-year-old male with primary prostate embryonal carcinoma. The patient received cisplatin-based chemotherapy. The patient refused a surgical treatment, which resulted in relapse of the disease and death in a short follow-up period. The present case shows that primary embryonal carcinoma may also be found in prostate and indicates the potential importance of timely surgical resection.

The Impact of Variant Histology in Patients with Urothelial Carcinoma Treated with Radical Cystectomy: Can We Predict the Presence of Variant Histology?

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.

Role of Healthcare Professionals and Sociodemographic Characteristics in COVID-19 Vaccination Acceptance among Uro-Oncology Patients: A Cross-Sectional Observational Study.

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.

Predictive Value of Inflammatory and Nutritional Indexes in the Pathology of Bladder Cancer Patients Treated with Radical Cystectomy.

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.

Polymorphisms of Antioxidant Enzymes SOD2 (rs4880) and GPX1 (rs1050450) Are Associated with Bladder Cancer Risk or Its Aggressiveness.

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.

Real World Overall Survival of Patients With Metastatic Renal Cell Carcinoma Treated With Only Available Sunitinib and Pazopanib in First-Line Setting.

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.

Role of AMPK/mTOR-independent autophagy in clear cell renal cell carcinoma.

We examined the status and role of autophagy, a process of lysosomal recycling of cellular material, in clear cell renal cell carcinoma (ccRCC). Paired samples of tumor and adjacent non-malignant tissue were collected from 20 patients with ccRCC after radical nephrectomy. The mRNA levels of apoptosis (BAD, BAX, BCL2, BCLXL, BIM) and autophagy (ATG4, BECN1, GABARAP, p62, UVRAG) regulators were measured by RT-qPCR. The protein levels of autophagosome-associated LC3-II, autophagy receptor p62, apoptotic marker PARP, as well as phosphorylation of autophagy initiator Unc 51-like kinase 1 (ULK1), its activator AMP-activated protein kinase (AMPK) and 4EBP1, the substrate of ULK1 inhibitor mechanistic target of rapamycin (mTOR), were analyzed by immunoblotting. The mRNA levels of pro-apoptotic BAX, anti-apoptotic BCLXL and pro-autophagic ATG4, p62 and UVRAG were higher in ccRCC tumors. Autophagy induction was confirmed by an increase in phospho-ULK1 and degradation of the autophagic target p62, while apoptotic PARP cleavage was unaltered. AMPK phosphorylation was reduced and 4EBP1 phosphorylation was increased in ccRCC tissue. The expression of apoptosis regulators did not correlate with clinicopathological features of ccRCC. Conversely, high mRNA levels of ATG4, GABARAP and p62 were associated with lower tumor stage, as well as with smaller tumor size and better disease-specific 5-year survival (ATG4 and p62). Accordingly, low p62 protein levels, corresponding to increased autophagic flux, were associated with lower tumor stage, reduced metastasis and improved 5-year survival. These data demonstrate that transcriptional induction of autophagy in ccRCC is accompanied by AMPK/mTOR-independent increase in ULK1 activation and autophagic flux, which might slow tumor progression and metastasis independently of apoptosis.

Association between GPX1 and SOD2 genetic polymorphisms and overall survival in patients with metastatic urothelial bladder cancer: a single-center study in Serbia.

PURPOSE: 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: 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 Kaplan­Meier survival analysis during 2-year follow up period, with the log-rank test for prognostic significance. RESULTS: 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: 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.

Pulsed versus continuous mode fluoroscopy during PCNL: safety and effectiveness comparison in a case series study.

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.

Penile fracture: a rare case of simultaneous rupture of the one corpus cavernosum and complete urethral rupture.

INTRODUCTION: Penile fracture is a traumatic rupture of tunica albuginea and the tumescent corpora cavernosa due to the nonphysiological bending of the penile shaft, presenting with or without rupture of corpus pongiosum and urethra. The incidence of concomitant injury of the urethra is 0-38%. Complete urethral rupture is rare, but it is almost always associated with bilateral corporeal injury. CASE REPORT: We presented a patient with complete urethral rupture, and rupture of the right cavernous body. According to the available literature, this case is extremely rare. CONCLUSION: Fracture of the penis is relatively uncommon and is considered a urologic emergency. Prompt surgical explo- ration and repair can preserve erectile and voiding function.

Testis sparing surgery in the treatment of bilateral testicular germ cell tumors and solitary testicle tumors: A single institution experience.

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.

Complications associated with percutaneous nephrolitholapaxy (PCNL)--our experience and literature review.

BACKGROUND: PCNL is safe procedure which is well tolerated, but as with any other surgical procedure, it is associated with a specific set of complications. There is a marked heterogeneity in reporting complication rates in literature, and this problem was highlighted in Ad Hoc EAU guidelines panel who recommended urgent creation of uniform and reproducible quality system. Modified Dindo-Clavien grading system today is the most utilized classification for complications in urology, and standard in reporting complications for PCNL. AIM(S): To analyze the complication rate for PCNL using the modified Dindo-Clavien grading system in our patients and literature review. METHODS: In our institution, with few breaks, PCNL was performed since mid 2010. Complication rate in 63 patients was analyzed retrospectively. Modified Dindo-Clavien grading system that is validated for PCNL has been accepted for classification of complication for PCNL, and literature review was performed. We have summarized the most significant factors which may affect the complication rate during and after PCNL. RESULTS: Overall complication rate was 30% in our study population. The most common complications observed were: postoperative fever Grade 1-2 (9.52%) and bleeding Grade l (7.9%), Grade 2 (3.17%), Grade 3a (4.76%) and Grade 3b (1.58%). Nephrostomy tube leakage was not found in our sample, mostly due to specific postoperative utilizing of auxiliary procedures. CONCLUSION: Reporting of complication for PCNL should be uniform, and modified Dindo-Clavien grading system that is validated for PCNL should be accepted to be a standard in urology. Surgeons training and experience are the most important to ensure the efficacy of procedure, therefore we suggest that learning of percutaneous renal access should be mandatory in residents trainee program.

Prognostic significance of non-muscle-invasive bladder tumor history in patients with upper urinary tract urothelial carcinoma.

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.

[Vesicovaginal fistulas: results of surgical treatment during ten years].

INTRODUCTION: Vesicovaginal fistulas (VVF) are the most common and the most frequent type of urogenital fistulas. They may have a different etiology. In most cases, surgery is required for treatment. OBJECTIVE: The aim of the study was to analyze the results of surgical therapy of VVF in a tertiary level institution over the last decade. METHODS: The retrospective study of results was conducted involving a total number of 99 women who were surgically treated for VVF at the Clinic of Urology of the Clinical Center of Serbia in Belgrade in the period from 2001-2010. RESULTS: Over the past ten years VVF occurred after hysterectomy in 74.7% of cases, and almost twice more frequently after hysterectomy for a benign gynecological disease. In the surgical treatment of primary VVF transvesical approach was used in 53.53% (52/99) of cases. Relapses were treated surgically using transperitoneal approach in all cases. No significant difference was found in respect to the applied approach in the surgical treatment of primary fistulas. In even 94% (93/99) of cases the problem of VVF was solved by a single surgical intervention only. In total, in 107 interventions 8 (7.4%) relapses were recorded. CONCLUSION: The study showed that VVF occurred after hysterectomy in three quarters of cases, more frequently after hysterectomy due to a benign gynecological disease. Early detection with timely and appropriate treatment of gynecological diseases will reduce the number of conditions that may lead to VVF. Surgical treatment of VVF yielded satisfactory results; it was shown that even in 94% of cases the problem of VVF was solved by a single surgical intervention only, however further improvement is certainly necessary.