Gennadi Tulchiner

Background: Renal cell carcinoma (RCC) is characterized by considerable heterogeneity and variable clinical outcomes. The identification of reliable biomarkers is crucial to improve prognostic assessment and therapeutic decision-making. CMTM6 (chemokine-like factor-like MARVEL transmembrane domain-containing protein 6) has emerged as a regulator of programmed death ligand-1 (PD-L1), a key immune checkpoint protein involved in tumor immune evasion. Objectives: The main objective of the study was to investigate the expression and prognostic significance of CMTM6 and to establish an automated immunohistochemical analysis. Design: This was a retrospective analysis conducted at a single center. Methods: Tumor samples from 111 patients who underwent partial nephrectomy for localized RCC between 2006 and 2019 were retrospectively analyzed. CMTM6 expression in tumor cells and tumor-infiltrating immune cells (ICs) was quantified using automated digital image analysis of immunohistochemically stained slides. Associations between CMTM6 expression, clinicopathological features, and patient outcomes were evaluated. Results: CMTM6 expression was heterogeneous across RCC samples, with significantly higher levels observed in clear cell RCC compared to non-clear cell subtypes. Elevated CMTM6 expression in ICs correlated with reduced overall survival ( p = 0.049) and shorter time to metastasis ( p = 0.009). Conversely, in patients with metastatic RCC receiving systemic therapy, lower CMTM6 expression was associated with shorter progression-free survival ( p = 0.047). However, lower CMTM6 scores were also significantly associated with more unfavorable outcome according to prognostic group defined by the Stage, Size, Grade, and Necrosis risk model for localized RCC. Conclusion: CMTM6 expression represents a promising prognostic biomarker in RCC, with differential associations depending on disease stage and treatment setting. Its correlation with established clinical risk classifications underscores its potential utility in prognostic refinement. Given its regulatory role in PD-L1 expression, CMTM6 may also represent a therapeutic target, with implications for optimizing immunotherapeutic strategies in RCC. Further validation in larger cohorts and prospective studies are warranted.

Background/Objectives: Reconstruction of membranous urethral strictures poses significant surgical challenges, including risks of urinary incontinence and erectile dysfunction. Optilume drug-coated balloon dilation (DCBD) is a minimally invasive treatment for short, recurrent bulbar urethral strictures, but its application in strictures involving the sphincteric urethra remains controversial. This study aims to evaluate the safety, efficacy, and impact on continence of DCBD in membranous urethral strictures involving the male sphincter. Methods: A retrospective analysis was conducted on 53 consecutive patients with urethral strictures involving the sphincteric urethra, treated with Optilume DCBD between June 2021 and June 2025 at a tertiary center. After preoperative imaging, dilation to 20 Fr, then DCBD (30 Fr, 10 bar, 10 min) were performed. We assessed anatomical success (≥18 Fr as per cystoscopy/calibration), freedom from re-intervention, and continence status. Patients with neurological conditions or urinary infections were excluded. Results: The cohort included 35 membranous urethral strictures and 18 vesicourethral anastomosis stenoses that extended into the sphincter. The median follow-up was 13.3 months. At last follow-up, 66.6% and 65.6% of patients in both groups were free from recurrence and re-intervention with satisfactory voiding. No de novo incontinence was observed; two patients with prior post-prostatectomy incontinence remained incontinent. The median age was 68 years; median prior interventions were 2.5, and median stricture length was 3 cm. Conclusions: Optilume DCBD appears to be a safe and effective option for membranous urethral strictures involving the sphincter, without inducing de novo incontinence. Although not a replacement for reconstruction, it offers a minimally invasive alternative for selected patients.

Background and Objectives: We aimed to assess the outcomes of upfront Optilume drug-coated balloon (DCB) dilation in patients after failed treatment for complex recurrent urethral stricture disease. All patients presented with acute urinary retention and were treated with DCB dilation regardless of stricture site and length. Materials and Methods: We retrospectively evaluated patients with acute urinary retention and known complex recurrent urethral strictures. Patients presented at the urology emergency room of our tertiary centre with an inability to void or a post-void residual (PVR) volume exceeding 400 mL between August 2021 and February 2024. Urethrography and/or endoscopic imaging confirmed the diagnosis. Patients with urinary tract infection/sepsis and those with neurological disease were excluded. Urethral dilation to 20 Fr was performed, followed by DCB dilation (30 Fr, 10 bar, 10 min). The primary endpoints were anatomical success (≥14 Fr by cystoscopy/calibration) at 12 months and freedom from repeat interventions. Results: Thirty-one consecutive male patients were evaluated, with twenty-six patients followed for ≥12 months (mean age 65 ± 16.8 years). The stricture sites included seven bulbopenile, seven bulbomembranous, seven anastomotic, three bladder neck, one penile, and one panurethral stricture. The median number of prior urethral/surgical interventions was 2 [IQR: 1–3] (range: 1–31). The median stricture length was 3 [IQR: 2–4] cm (range: 1–8). At 12 months, 65.4% (17/26) of subjects voided satisfactorily and were free of recurrence and reoperation. Conclusions: Timely DCB dilation may offer a viable treatment option for patients with complex recurrent urethral strictures and urinary retention, particularly those who are unable or unwilling to undergo surgical reconstruction and prefer to avoid indwelling catheters.

Objective: To assess the outcomes of upfront Optilume drug-coated balloon (DCB) treatment in patients after failed treatment for complex recurrent urethral stricture disease. All patients presented with acute urinary retention, and were treated with DCB dilation regardless of stricture site/length. Patients and Methods: We retrospectively evaluated patients with acute urinary retention and known complex recurrent urethral strictures. Patients presented at the urology emergency room of our tertiary centre with an inability to void or a post-void residual (PVR) exceeding 400 ml between August 2021 and February 2024. Urinary tract infection was immediately excluded, and urethrography and/or endoscopic imaging confirmed the diagnosis of urethral stricture. Urethral dilation to 20 Fr was performed, followed by drug-coated balloon dilation (30 Fr, 10 bar, 10 minutes). The primary endpoints were anatomical success (≥14 Fr by cystoscopy/calibration) at 12 months and freedom from repeat interventions. Patients requiring suprapubic catheterisation for UTI/sepsis and those with neurological disease were excluded. Results: Thirty-one consecutive male patients were evaluated, with 26 patients followed for ≥ 12 months (mean age 65 ± 16.8 years). Stricture sites: seven bulbopenile, seven bulbomembranous, seven anastomotic, three bladder neck, one penile, and one panurethral. The median number of prior urethral/surgical interventions was 2 [IQR: 1-3] (range: 1-31). The median stricture length was 3 [IQR: 2-4] cm. (range: 1-8). At 12 months 65.4% (17/26) of subjects voided satisfactorily, free of recurrence and reoperation. Conclusions: Nearly two-thirds of multimorbid patients with previously treated complex recurrent urethral strictures had a patent urethra at 12 months after a single treatment with DCB dilatation. Optilume dilation offers a viable treatment option for patients with complex recurrent urethral strictures and urinary retention, particularly those who are unable or unwilling to undergo surgical reconstruction and prefer to avoid indwelling urethral catheters.

Kidney cancer is a common malignancy that constitutes around 5% of all cancer cases. Males are twice as likely to acquire renal cell carcinoma (RCC) compared to females and experience a higher rate of mortality. These disparities indicate that sex hormone (SH)-dependent pathways may have an impact on the aetiology and pathophysiology of RCC. Examination of SH involvement in conventional signalling pathways, as well as genetics and genomics, especially the involvement of ribonucleic acid, reveal further insights into sex-related differences. An understanding of SHs and their influence on kidney cancer is essential to offer patients individualized medicine that would better meet their needs in terms of prevention, diagnosis and treatment. This review presents the understanding of sex-related differences in the clinical manifestation of kidney cancer patients and the underlying biological processes.

Current guidelines recommend repeat computed tomography (CT) imaging in high-grade blunt renal injury within 48–96 h, yet diagnostic value and clinical significance remain controversial. The aim of this work was to determine the possible gain of CT re-imaging in uncomplicated patients with blunt renal trauma at 48 h after injury, presenting one of the largest case series. A retrospective database of patients admitted to our centre with isolated blunt renal trauma due to sporting injuries was analysed for a period of 20 years (2000–2020). We included only patients who underwent repeat imaging at 48 h after trauma irrespective of AAST renal injury grading (grade 1–5) and initial management. The primary outcome was intervention rates after CT imaging at 48 h in uncomplicated patients versus CT scan at the time of clinical symptoms. A total of 280 patients (mean age: 37.8 years; 244 (87.1%) male) with repeat CT after 48 h were included. 150 (53.6%) patients were classified as low-grade (grade 1–3) and 130 (46.4%) as high-grade (grade 4–5) trauma. Immediate intervention at trauma was necessary in 59 (21.1%) patients with high-grade injuries: minimally invasive therapy in 48 (81.4%) and open surgery in 11 (18.6%) patients, respectively. In only 16 (5.7%) cases, intervention was performed based on CT re-imaging at 48 h (low-grade vs. high-grade: 3.3% vs. 8.5%; p = 0.075). On the contrary, intervention rate due to clinical symptoms was 12.5% (n = 35). Onset of clinical progress was on average (range) 5.3 (1–17) days post trauma. High-grade trauma (odds ratio [OR]_{grade 4 vs. grade 3}, 14.62; p < 0.001; OR_{grade 5 vs. grade 3}, 22.88, p = 0.004) and intervention performed at the day of trauma (OR 3.22; p = 0.014) were powerful predictors of occurrence of clinical progress. Our data suggest that routine CT imaging 48 h post trauma can be safely omitted for patients with low- and high-grade blunt renal injury as long as they remain clinically stable. Patients with high-grade renal injury have the highest risk for clinical progress; thus, close surveillance should be considered especially in this group.

Platinum-based chemotherapy is the standard of care with concern to first-line systemic therapy for metastatic disease in urothelial cancer (UC). Resistance to chemotherapy despite an initial response is linked with the ability to remove platinum-based DNA adducts and to repair chemotherapy-induced DNA lesions by various DNA repair proteins. The Rad9-Rad1-HUS1 complex that is loaded onto DNA at sites of damage is involved in checkpoint activation as well as DNA repair. Here, we addressed for the first time the potential influence of HUS1 expression in urothelial carcinogenesis (using two human basal urothelial cancer cell lines UM-UC-3 and HT1197) and its role as a potential therapeutic target for predicting responses to platinum-based chemotherapy. Specific inhibition of HUS1 expression in both cell lines was achieved by specific siRNA and validated by Western blot. In order to define the possible importance of HUS1 in the regulation of cellular proliferation, parental and resistant cells were treated with increasing concentrations of either control or HUS1 siRNA. HUS1 protein expression was observed in both human basal urothelial cancer cell lines UM-UC-3 and HT1197. In cisplatin-sensitive cells, knock-down of HUS1 inhibited cellular proliferation in the presence of cisplatin. On the contrary, knock-down of HUS1 in resistant cells did not result in a re-sensitization to cisplatin. Finally, RNAseq data from the Cancer Genome Atlas provided evidence that HUS1 expression is a significant prognostic factor for poor survival in UC patients. In summary, HUS1 may acts as an oncogene in UC and might be a key determinant of the cellular response to cisplatin-based chemotherapy.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr–Sep) and an increase during the winter months (Oct–Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct–Dec (p = 0.008) and Jan–Mar (p < 0.001) was significantly higher compared to the months of Jul–Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (β-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and β-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.