Multifocality in Testicular Cancer: Clinicopathological Correlations and Prognostic Implications.

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.

Prognostic Impact of Preoperative Thrombocytosis on Recurrence-Free Survival in Patients with Upper Tract Urothelial Carcinoma.

BACKGROUND: The aim of this work was to evaluate the prognostic potential of preoperative thrombocytosis for recurrence-free survival (RFS) and cancer-specific survival (CSS) among patients subjected to radical nephroureterectomy (RNU) due to UTUC. PATIENTS AND METHODS: Analytical cohort was composed of a single-center series of 405 patients treated between January 1999 and December 2020. Thrombocytosis was defined as a platelet count exceeding the threshold value of 400 × 109 per L. Along with the Kaplan-Meier survival probability, Cox proportional hazard regression models were used. RESULTS: Preoperative thrombocytosis confirmed in 71 patients (17.5%) was significantly associated with the higher pathological tumor stage, lymph node metastasis, prior bladder cancer diagnosis, and preoperative anemia. With a median post-surgical follow-up period of 33.5 months, 125 patients (30.9%) experienced disease recurrence. The recurrence rate among patients with normal platelet levels was 13.6%, compared with 22.2% in those with preoperative thrombocytosis (p < 0.03). The 5-year RFS estimates reached 36.6% in the thrombocytosis-confirmed group. Multivariate analysis implied that preoperative thrombocytosis was a significant independent prognosticator of both poor RFS (HR 2.22, 95% CI 1.14-4.31, p = 0.02) and CSS (HR 2.48, 95% CI 1.14-3.09, p = 0.01). CONCLUSIONS: Patients with a clinically significant elevation of platelet count prior to RNU were more likely to have UTUC with advanced tumor stages and lymph node metastases. Preoperative thrombocytosis was an independent predictor of RFS and CSS in patients who underwent radical nephroureterectomy. Furthermore, preoperative thrombocytosis may complement and refine UTUC clinical prediction algorithms as an independent indicator of adverse survival outcomes.

Prognostic value of preoperative De Ritis ratio on oncological outcomes in patients with muscle-invasive bladder cancer.

OBJECTIVE: We aimed to assess the prognostic value of De Ritis ratio on oncological outcomes in patients suffering from urothelial bladder cancer and undergoing radical cystectomy (RC). PATIENTS AND METHODS: Analytical cohort comprised a single-center series of 367 patients treated between January 2015 and December 2018. Patients were classified into two groups based on De Ritis ratio (<1.3 [normal] vs. ≥1.3 [high]). Along with the Kaplan-Meier survival probability, cox proportional hazard regression models were used. RESULTS: A total of 299 patients were included, 60.5% of them having a De Ritis ratio of <1.3% and 39.5% with a De Ritis ratio of ≥1.3. Preoperative increased De Ritis ratio was associated with age (p = 0.001), gender (p = 0.044), cancer-related death (p = 0.001), overall death (p = 0.001), and tumor stage (p = 0.001). Multivariate analysis implied that preoperative De Ritis ratio was a significant independent prognosticator of overall survival (HR 0.461; 95% CI 0.335-0.633; p < 0.001) and CSS (HR 0.454; 95% CI 0.330-0.623; p < 0.001). Only tumor stage (HR 1.953; 95% CI 1. 106-3.448; p = 0.021) was independently associated with recurrence-free survival (RFS). De Ritis ratio was not independently associated with RFS in multivariate analyses. During the follow up, a total of 198 (66.2%) patients died, including 173 (57.9%) from BC, 5-year CSS was 45.8%. CONCLUSIONS: De Ritis ratio is an independent prognostic factor of cancer specific and overall survival in patients treated with RC for urothelial BC. RC patients may benefit from the use of the De Ritis ratio as a valid predictive biomarker.

Diagnostic and prognostic impact of preoperative thrombocytosis in muscle invasive bladder cancer: Any role in clinical practice?

BACKGROUND: Since earlier research suggested a link between preoperative thrombocytosis and poor oncological outcomes in several cancers, the significance of platelet count abnormalities in bladder carcinoma (BC) demands for further investigation. OBJECTIVE: To assess the prognostic value of preoperative thrombocytosis (PTC) on survival in patients with bladder carcinoma treated by radical cystectomy (RC). PATIENTS AND METHODS: Analytical cohort comprised a single-center series of 299 patients who underwent RC for bladder carcinoma was evaluated. A platelet count beyond the threshold of 400 × 109 /L was considered thrombocytosis. Along with the Kaplan-Meier survival probability, cox proportional hazard regression models were used. RESULTS: Twenty-eight (9.4%) patients had preoperative thrombocytosis. PTC was associated with gender, tumor stage, tumor grade, lymphovascular invasion, hydronephrosis, anemia (p < 0.001), and hypoalbuminemia (p < 0.001). Preoperative thrombocytosis was strongly linked to worse overall survival (OS) (p = 0.002), and cancer specific survival (CSS) (p = 0.004), according to the Kaplan-Meier method. Throughout the follow-up, a total of 198 (66.2%) patients died, including 170 (56.9%) from BC. For this study population 5-year CSS was 45.8%. Preoperative thrombocytosis was not independently associated with OS (HR 1.168; 95% CI 0.740-1.844; p = 0.504) or CSS (HR 1.060; 95% CI 0.649-1.730; p = 0.816) in multivariate Cox regression analysis. Only tumor stage (HR 2.558; 95% CI 1.675-3.908; p < 0.001), hydronephrosis (HR 1.614; 95% CI 1.173-2.221; p = 0.003), lymph node metastasis (HR 1.555; 95% CI 1.076-2-2.248; p = 0.019), anemia (HR 1.454; 95% CI 1.034-2.046; p = 0.032) and ASA grade (HR 1.375; 95% CI 1.006-1.879; p = 0.046) were independently associated with CSS. CONCLUSIONS: In a single-center study of consecutive patients who underwent radical cystectomy for bladder cancer, preoperative thrombocytosis was unable to predict outcomes.

The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study.

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.

Prognostic Significance of Systemic Inflammation Markers in Testicular and Penile Cancer: A Narrative Review of Current Literature.

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.

The Role of Isoflavones in the Prevention of Breast Cancer and Prostate Cancer.

This narrative review summarizes epidemiological studies on breast cancer and prostate cancer with an overview of their global incidence distribution to investigate the relationship between these diseases and diet. The biological properties, mechanisms of action, and available data supporting the potential role of isoflavones in the prevention of breast cancer and prostate cancer are discussed. Studies evaluating the effects of isoflavones in tissue cultures of normal and malignant breast and prostate cells, as well as the current body of research regarding the effects of isoflavones attained through multiple modifications of cellular molecular signaling pathways and control of oxidative stress, are summarized. Furthermore, this review compiles literature sources reporting on the following: (1) levels of estrogen in breast and prostate tissue; (2) levels of isoflavones in the normal and malignant tissue of these organs in European and Asian populations; (3) average concentrations of isoflavones in the secretion of these organs (milk and semen). Finally, particular emphasis is placed on studies investigating the effect of isoflavones on tissues via estrogen receptors (ER).

Alteration of Lipid Metabolism in Prostate Cancer: Multifaceted Oncologic Implications.

Cancer is increasingly recognized as an extraordinarily heterogeneous disease featuring an intricate mutational landscape and vast intra- and intertumor variability on both genetic and phenotypic levels. Prostate cancer (PCa) is the second most prevalent malignant disease among men worldwide. A single metabolic program cannot epitomize the perplexing reprogramming of tumor metabolism needed to sustain the stemness of neoplastic cells and their prominent energy-consuming functional properties, such as intensive proliferation, uncontrolled growth, migration, and invasion. In cancerous tissue, lipids provide the structural integrity of biological membranes, supply energy, influence the regulation of redox homeostasis, contribute to plasticity, angiogenesis and microenvironment reshaping, mediate the modulation of the inflammatory response, and operate as signaling messengers, i.e., lipid mediators affecting myriad processes relevant for the development of the neoplasia. Comprehensive elucidation of the lipid metabolism alterations in PCa, the underlying regulatory mechanisms, and their implications in tumorigenesis and the progression of the disease are gaining growing research interest in the contemporary urologic oncology. Delineation of the unique metabolic signature of the PCa featuring major aberrant pathways including de novo lipogenesis, lipid uptake, storage and compositional reprogramming may provide novel, exciting, and promising avenues for improving diagnosis, risk stratification, and clinical management of such a complex and heterogeneous pathology.

Interplay between Comprehensive Inflammation Indices and Redox Biomarkers in Testicular Germ-Cell Tumors.

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 Polymorphisms of Genes Encoding Catalytic Antioxidant Proteins Modulate the Susceptibility and Progression of Testicular Germ Cell Tumor.

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.

Coronary revascularisation outcome questionnaire: validation study of the Serbian version.

PURPOSE: To translate, culturally adapt and validate the Coronary Revascularisation Outcome Questionnaire (CROQ), a disease-specific tool for measuring health-related quality of life (HRQoL) in patients with ischaemic heart disease (IHD), into Serbian language (CROQ-S). METHODS: Validation study was performed at the Clinic for Cardiac Surgery and Clinic for Cardiology, University Clinical Centre of Serbia. We included a convenience sample of 600 patients with IHD divided into four groups. Acceptability, reliability and validity of the CROQ-S were assessed. RESULTS: CROQ-S was acceptable to patients as demonstrated by less than 1% of missing data for each single item. Cronbach's Alpha was higher than the criterion of 0.70 for all scales in each version except the Cognitive Functioning scale which only met this criterion in the CABG pre-revascularisation version. Mean values of item-total correlations were greater than 0.30 for all scales except the Cognitive Functioning scale in both the pre-revascularisation groups. Compared to the original version, exploratory factor analysis in our study showed more factors; however, the majority of items had a factor loading greater than 0.3 on the right scale. Correlations of CROQ-S scales with the 36-Item Short Form Health Survey and Seattle Angina Questionnaire showed the expected pattern whereby scales measuring similar constructs were most highly correlated. CONCLUSION: CROQ-S is an acceptable, reliable and valid disease-specific instrument for measuring HRQoL in this sample of Serbian speaking patients with IHD both before and after coronary revascularisation. However, the Cognitive Functioning scale did not meet all the psychometric criteria and further validation of its responsiveness is required.

Treatment options in stage I seminoma.

Seminomas are most commonly diagnosed in clinical stage I (CSI). After orchiectomy, approximately 15% of patients in this stage have subclinical metastases. Adjuvant radiotherapy (ART) delivered to the retroperitoneum and ipsilateral pelvic lymph nodes has been the mainstay of treatment for many years. Although highly efficient, with long-term cancer-specific survival (CSS) rates approaching almost 100%, ART is associated with considerable long-term consequences, particularly cardiovascular toxicity and increased risk of secondary malignancies (SMN). Therefore, active surveillance (AS) and adjuvant chemotherapy (ACT) were developed as alternative treatment options. While AS prevents patient overtreatment, it is associated with strict follow-up regimens and increased radiation exposure due to repeated imaging. Due to equivalent CSS rates to ART, and lower toxicity, one course of adjuvant carboplatin presents the cornerstone of chemotherapy for CSI patients. CSS is almost 100% for patients with CSI seminoma, regardless of the chosen treatment option. Therefore, a personalized approach in treatment selection is preferred. Currently, routine radiotherapy for CSI seminoma patients is no longer recommended. Instead, it should be reserved for patients who are unfit or unwilling for AS or ACT. Identification of prognostic factors for disease relapse allowed for the development of risk-adapted treatment strategy and stratification of patients in low-risk and high-risk groups. Although risk-adapted policy needs further validation, surveillance is currently recommended in low-risk patients, while ACT is reserved for patients with a higher risk of relapse.

Prognostic value of Balkan endemic nephropathy and gender on upper tract urothelial carcinoma outcomes after radical nephroureterectomy: A cohort study.

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.

Prognostic significance of tumor multifocality on outcomes in patients with upper tract urothelial carcinoma after radical nephroureterectomy: A cohort study.

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.

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.

GSTP1 rs1138272 Polymorphism Affects Prostate Cancer Risk.

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.

Repair of urethral injury associated with penile fracture using buccal mucosa graft: A novel therapeutic approach for complex cases.

Penile fracture is a rare urological emergency caused by blunt trauma to the erect penis and it may be accompanied by urethral injury. Complete urethral rupture is very uncommon and is usually managed by primary anastomosis. However, these patients are more likely to develop post-operative complications such as urethral strictures. Buccal mucosa graft is commonly used for substitution urethroplasty in management of urethral strictures, but its use has not been reported for immediate treatment in the setting of penile fracture. We report a patient with rupture of both corpora cavernosa, as well as the rupture of the urethra, after sexual intercourse. Buccal mucosa graft was used for surgical repair of urethral injury. At 36-month follow-up patient did not experience erectile or voiding problems. The application of this technique could possibly reduce the incidence of urethral strictures in these patients and further prospective studies with larger samples should be conducted.