Aleksandar Janicic

Background: Considering the high global frequency of prostate cancer, it is necessary to know the benefits and drawbacks of numerous diagnostic and therapeutic modalities. Methods: In this article, we include 88 manuscripts (46/88 original studies) found on PubMed, written in English in extenso, dealing with nuclear medicine methods in patients with prostate cancer. Results: Choline PET/CT had low sensitivity in detecting the primary tumor. This method has been almost completely replaced by PSMA PET/CT, which is included in international guidelines and recommended for initial staging of unfavorable intermediate- to high-risk prostate cancer, the detection of recurrent disease after treatment, the evaluation of mCRPC, therapy response evaluation, and theranostics. FDG is currently used in aggressive forms of prostate cancer and as a supplement in PSMA PET/CT for patient selection for RLT. Na[¹⁸F]F has demonstrated satisfactory diagnostic capacity for evaluating bone loss; however, due to a lack of research, it is not recommended in international guidelines. ¹⁸F-Fluciclovine has lower sensitivity than [¹⁸F]F-PSMA-1007 for the detection of early biochemical recurrence in prostate cancer. GRPR and SSTR analogs are less frequently used but can be useful in the evaluation of rarer pathohistological types. [^99mTc]Tc-PSMA can be used in resource-limited settings where PET/CT is unavailable, with a lower sensitivity compared to [¹⁸F]F-PSMA-1007 but a higher sensitivity compared to bone scans. Conclusions: PSMA tracers are important tools for evaluating intermediate- and high-risk prostate cancer, with limitations in 5–10% of prostate cancers that do not express PSMA. Theranostics are increasingly incorporating PSMA.

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.

Background: Hemoglobin, Albumin, Lymphocyte, and Platelet Score (HALP) is an accessible score that is easily reproducible from routine laboratory testing while also reflecting patients’ immune-nutritional status. Along with other immuno-nutritional scores, such as the Prognostic Nutrition Index (PNI), HALP has been associated with a number of clinical and pathological features. The goal of our study was to evaluate the prognostic utility of HALP and PNI scores in testicular germ cell cancer (GCT) patients. Methods: This case-only study included 203 testicular GCT patients who were classified according to the disease stage and HALP and PNI cut-offs. Complete blood count and albumin concentration were routinely determined. Results: The values of HALP and PNI significantly differed among different clinical stages (p < 0.05). Moreover, they clearly exposed a significantly higher risk of advanced clinical stage development for those testicular GCT patients with lower values of HALP and PNI (p < 0.05). Finally, lower score levels were associated with larger tumor size (p < 0.05). Conclusion: Our investigation could provide evidence that specific immune-nutritional scores can help distinguish individuals diagnosed with testicular GCT who are more likely to be identified with advanced disease stages.

There are limited data regarding the significance of multifocality in testicular cancer patients. This study evaluated the relationship between multifocality and clinicopathological features determined at the time of radical orchiectomy. The study involved 280 consecutive patients who underwent radical orchiectomy between 2018 and 2023. Multifocality was defined as a distinct tumor focus characterized by a group of malignant cells > 1 mm, clearly differentiated from the primary tumor mass. Uni- and multivariate logistic regression analyses were employed to investigate the association between multifocality and histopathological parameters along with potential risk factors for clinical stages II + III. Multifocality was identified in 44 (15.7%) patients. Significantly smaller primary tumors were observed in subjects with multifocality (20.0 mm vs. 30.0 mm, p = 0.0001), while those exhibiting monofocality presented a markedly elevated rate of tumors exceeding 4 cm (40.3% vs. 18.2%, p = 0.005). Furthermore, multifocality was associated with a significantly higher rate of primary tumors < 2 cm (52.3% vs. 29.2%, p = 0.003). Univariate logistic regression analysis revealed a substantial decrease in the likelihood of multifocality occurrence in seminoma patients with tumors > 4 cm (OR = 0.38, p = 0.017). Meanwhile, in multivariate logistic regression, multifocality did not emerge as a significant risk factor for clinical stages II + III in either seminoma (p = 0.381) or non-seminoma (p = 0.672) cases. Our study suggests that multifocality holds no substantial prognostic relevance for clinically advanced disease in testicular cancer patients. The findings indicate that multifocality is associated with smaller primary tumors, particularly those measuring less than 2 cm.

Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of GSTO1rs4925, GSTO2rs156697, and GSTO2rs2297235 polymorphisms with the risk for testicular GCT development, in 88 patients and 96 matched controls, through logistic regression models. We found that carriers of the GSTO1*C/A*C/C genotype exhibited an increased risk for testicular GCT development. Significant association with increased risk of testicular GCT was observed in carriers of GSTO2rs2297235*A/G*G/G genotype, and in carriers of combined GSTO2rs156697*A/G*G/G and GSTO2rs2297235*A/G*G/G genotypes. Haplotype H7 (GSTO1rs4925*C/GSTO2rs2297235*G/GSTO2rs156697*G) exhibited higher risk of testicular GCT, however, without significant association (p > 0.05). Finally, 51% of testicular GCT patients were the carriers of all three risk-associated genotypes, with 2.5-fold increased cumulative risk. In conclusion, the results of this pilot study suggest that GSTO polymorphisms might affect the protective antioxidant activity of GSTO isoenzymes, therefore predisposing susceptible individuals toward higher risk for testicular GCT development.

In contemporary clinical practice, biomarkers are indispensable in the assessment and management of oncological patients. Although established serum tumor markers (beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP), and lactate dehydrogenase (LDH)) have an indisputably important role in the management of patients with testicular cancer (TC), the application of these tumor markers may be accompanied with certain limitations, implying the need for additional biomarkers. Contrary to TC, there is a lack of established serological biomarkers for penile cancer (PC) and the management of this urological malignancy is based on multiple clinicopathological parameters. Therefore, the identification and rigorous analytical and clinical validation of reliable biomarkers are considered pivotal for improving PC management. Inflammation may be associated with all stages of oncogenesis, from initial neoplastic transformation to angiogenesis, tissue invasion, and metastasis. Accordingly, an array of inflammation-related indices have gained increasing attention as emerging predictors of oncological outcomes. The clinical usefulness of systemic inflammation markers was reported in many urological and non-urological malignancies. The aim of this narrative review is to summarize current scientific data regarding the prognostic and predictive significance of systemic inflammation markers in TC and PC patients.

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.

The simultaneous analysis of redox biomarkers and polymorphisms encoding for regulatory and catalytic antioxidant proteins was performed in order to evaluate their potential role in the development of testicular germ cell tumor (GCT), as well as the progression of the disease. NRF2 (rs6721961), GSTM3 (rs1332018), SOD2 (rs4880) and GPX3 (rs8177412) polymorphisms were assessed in 88 patients with testicular GCT (52 with seminoma) and 88 age-matched controls. The plasma levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), thiol groups and the plasma activity of glutathione peroxidase were measured. A significant association between variant GPX3*TC+CC genotype and risk of overall testicular GCT, as well as seminoma development, was found. Moreover, carriers of variant SOD2*TT genotype were at almost 3-fold increased risk of seminoma development. Interestingly, combined SOD2*TT/GPX3*TC+CC genotype conferred a 7-fold higher risk for testicular GCT development. Finally, variant GSTM3*AC+CC genotype was associated with a higher risk for the development of advanced diseased. The presence of assessed genetic variants was not associated with significantly higher levels of redox biomarkers in both testicular GCT patients, as well as in those diagnosed with seminoma. In conclusion, the polymorphic expression of certain antioxidant enzymes might affect susceptibility toward testicular GCT development, as well as the progression of the disease.

Wegener's granulomatosis (WG) is a systemic disorder characterized by necrotizing vasculitis involving the respiratory tract, and in most cases, the kidneys. The most common manifestation of WG in the kidneys is segmental necrotizing glomerulonephritis. The presence of a renal mass as a manifestation of WG is rare. We report a patient with WG in whom a CT scan revealed an infiltrating mass in the lower portion of the left kidney. After surgical exploration, we performed an open radical nephrectomy. Histopathology showed clear cell type renal cell carcinoma (RCC). RCC associated with WG has been reported in only a few cases, and in most of them, the diseases started simultaneously, suggesting common pathogenetic pathways. Long-term immunosuppressive treatment is a known risk factor in the development of malignancies, so occurrence of RCC in WG has been proposed as a side effect of cyclophosphamide treatment. Furthermore, it is important to make a differential diagnosis between RCC and pseudotumors in WG as they cannot be distinguished solely on basis of imaging findings. Due to the higher risk of urologic malignancies, more frequent checkups and screening of WG patients should be considered.