Search Results (153)

Robotic retroperitoneal lymph node dissection (R-RPLND) represents an evolution in the surgical management of testicular germ cell tumors, offering reduced morbidity compared with open approaches. However, this procedure remains technically challenging, particularly after chemotherapy, due to dense fibrosis and distortion of the retroperitoneal anatomy. We report a case of an unrecognized intraoperative thermal injury causing a partial transection of the proximal ureter presenting postoperatively as a urinary fistula following R-RPLND for residual mass resection, along with a focused review of the contemporary literature on procedure-related complications. A review of large series highlights severe complications (Clavien–Dindo ≥ III) occurring in 6–12% of cases, with ureteral injuries occurring in up to 6%, often identified after surgery. This case underscores the importance of meticulous dissection, awareness of altered anatomy, and prompt intervention when unexpected events arise during R-RPLND. Full article

Background and Objectives: Radiomics and artificial intelligence (AI) offer emerging quantitative tools for enhancing the diagnostic evaluation of testicular cancer. Conventional imaging—ultrasound (US), magnetic resonance imaging (MRI), and computed tomography (CT)—remains central to management but has limited ability to characterize tumor subtypes, detect occult nodal disease, or differentiate necrosis, teratoma, and viable tumor in post-chemotherapy residual masses. This systematic review summarizes current advances in radiomics and AI for both primary tumors and retroperitoneal disease. Materials and Methods: A systematic search of PubMed, Scopus, and Web of Science identified studies applying radiomics or AI to testicular tumors, retroperitoneal lymph nodes and post-chemotherapy residual masses. Eligible studies included quantitative imaging analyses performed on ultrasound, MRI, and CT, with optional integration of clinical or molecular biomarkers. Eighteen studies met inclusion criteria and were evaluated with respect to methodological design, diagnostic performance, and translational readiness. Results: Across modalities, radiomics demonstrated encouraging discriminatory capacity, with accuracies of 74–82% for ultrasound, 80.7–97.9% for MRI, and 71.7–85.3% for CT. CT-based radiomics for post-chemotherapy residual masses showed moderate ability to distinguish necrosis/fibrosis, teratoma, and viable germ-cell tumor, though heterogeneous methodologies and limited external validation constrained generalizability. The strongest performance was observed in multimodal approaches: integrating radiomics with clinical variables or circulating microRNAs improved accuracy by up to 12% and 15%, respectively, mirroring gains reported in other oncologic radiomics applications. Persisting variability in segmentation practices, acquisition protocols, feature extraction, and machine-learning methods highlights ongoing barriers to reproducibility. Conclusions: Radiomics and AI-enhanced frameworks represent promising adjuncts for improving the noninvasive evaluation of testicular cancer, particularly when combined with clinical or molecular biomarkers. Future progress will depend on standardized imaging protocols, harmonized radiomics pipelines, and multicenter prospective validation. With continued methodological refinement and clinical integration, radiomics may support more precise risk stratification and reduce unnecessary interventions in testicular cancer. Full article

This study explores the effects of exogenous SELENOV on cellular migration, viability, mitochondrial function, ROS production, and Ca²⁺ signaling in mouse fibroblast L-929 and testicular teratoma F-9 cells. In scratch assays, 50–100 µg/mL SELENOV significantly inhibited F-9 cell migration after 48 h, while in L-929 fibroblasts, only 100 µg/mL had a suppressive effect. Viability assays revealed strong cytotoxicity in F-9 cells. Critically, at a dose of 50 µg/mL (where the corresponding volume of solvent buffer alone was non-toxic), SELENOV reduced survival to 19%, triggering late apoptosis in 76% of cells, whereas in L-929 cells, comparable effects required 100 µg/mL. Mitochondrial depolarization (JC-1/Rhodamine-123 assays) was pronounced in F-9 cells even at 50 µg/mL, while L-929 cells responded only to 100 µg/mL. Similarly, 50 µg/mL SELENOV induced significant ROS overproduction in F-9 but not in L-929 cells, correlating with upregulated NOX1, NOX4, GPX3, and GPX4 expression. Ca²⁺ imaging showed dose-dependent [Ca²⁺]ᵢ elevation, with 50 µg/mL SELENOV inducing a sustained rise in F-9 cells, whereas L-929 cells required higher doses. Strikingly, 50 µg/mL SELENOV in F-9 cells downregulated BCL-2 and BCL-xL while upregulating pro-apoptotic BAX and PUMA, suggesting selective activation of intrinsic apoptosis. These results demonstrate that F-9 cancer cells are significantly more sensitive to SELENOV than normal fibroblasts, with 50 µg/mL sufficient to trigger mitochondrial dysfunction, oxidative stress, and apoptosis. The findings highlight SELENOV’s potential as a targeted anticancer agent, particularly for germ cell tumors. Full article

Hereditary predisposition substantially shapes prevention and management across urologic oncology. This narrative review synthesizes contemporary, practice-oriented guidance on whom to test, what to test, how to act on results, and how to implement care equitably for hereditary forms of prostate cancer, renal cell carcinoma (RCC), urothelial carcinoma, pheochromocytoma/paraganglioma (PPGL), and adrenocortical carcinoma (ACC). We delineate between forms of indication-driven germline testing (e.g., universal testing in metastatic prostate cancer; early-onset, bilateral/multifocal, or syndromic RCC; reflex tumor mismatch repair (MMR)/microsatellite instability (MSI) screening in upper-tract urothelial carcinoma (UTUC); universal testing in PPGL; universal TP53 testing in ACC) and pair these strategies with minimum actionable gene sets and syndrome-specific surveillance frameworks. Key points include targeted prostate-specific antigen screening in BRCA2 carriers and the impact of BRCA/ATM variants on reclassification during active surveillance; major hereditary RCC syndromes with genotype-tailored surveillance and pathway-directed therapy (e.g., HIF-2α inhibition for von Hippel–Lindau disease); UTUC/bladder cancer in Lynch syndrome with tumor MMR/MSI screening, annual urinalysis (selective cytology), and immunotherapy opportunities in deficient MMR disease/MSI-H; PPGL management emphasizing universal germline testing, intensified surveillance for SDHB, cortical-sparing adrenalectomy, and emerging HIF-2α inhibition; and ACC care modified by Li–Fraumeni syndrome (minimization of radiation/genotoxic therapy with whole-body imaging surveillance). Testicular germ cell tumor remains largely polygenic, with no routine germline testing in typical presentations. Finally, we provide pre-/post-test genetic-counseling checklists and mainstreamed workflows with equity metrics to operationalize precision care and close real-world access gaps. Full article

Background and Objectives: Malignant germ cell tumors (GCTs) are rare but clinically significant neoplasms arising in gonadal and extragonadal sites. Malignant GCTs, divided into seminomatous and non-seminomatous subtypes, show diverse biological behavior. Although molecular studies have advanced understanding of their origins and genetic features, little is known about metastatic patterns due to their rarity and generally favorable outcomes. This study aimed to describe metastatic patterns of malignant GCTs across primary sites and histologic subtypes using population-based database. Materials and Methods: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) program for patients diagnosed with malignant GCTs between 2010 and 2022. Cases were stratified by primary site (testis, ovary, mediastinum), age group (<8 years vs. ≥8 years), and histologic subtype. Metastatic patterns were assessed using both overall and organotropic metastasis rates, and differences between groups were evaluated descriptively using appropriate statistical tests. Results: A total of 32,015 malignant GCTs were identified, comprising 93.0% testicular, 5.6% ovarian, and 1.4% mediastinal tumors. In patients aged ≥8 years, ovarian tumors tended to show generally lower lymph node and distant metastasis rates. In contrast, mediastinal tumors appeared to have the highest distant metastasis rates. Organotropic analysis suggested distinct subtype- and site-specific differences. For seminoma/dysgerminoma, the organotropic metastasis pattern was generally consistent across different primary sites, whereas the other subtypes showed variable organotropic metastasis rates depending on the primary site. Conclusions: The metastatic patterns of GCTs appear to differ by histologic subtype and primary site. These findings suggest that both subtype and site of origin should be considered when assessing metastatic risk and may provide a framework for improved risk stratification in clinical practice. Full article

Background: Spontaneous regression of testicular cancer with retroperitoneal metastasis is a rare phenomenon and poses challenges in its diagnosis. Methods: A 33-year-old male patient presented with severe lower back pain (10/10) of 4 months’ duration, radiating to the left lower limb, refractory to NSAIDs, and significantly impaired ambulation, accompanied by nausea and vomiting. In addition to difficulty initiating urination and defecation, with weight loss of 30 kg, he was referred to the urology service of our hospital. Results: On physical examination, the left testicle showed signs of varicocele without pain. Therefore, laboratory and imaging studies were requested, highlighting elevated β-hCG (156.4 mIU/mL) and LDH (850 IU/L). Testicular ultrasound confirmed the diagnosis of left varicocele, while computed tomography of the abdomen and pelvis with contrast revealed a conglomerated retroperitoneal mass of more than 5 cm, located in the paravertebral, retrocural, paraaortic, and intercavoaortic regions. Based on these findings, primary treatment with left radical orchiectomy was chosen, which showed regression of the seminomatous tumor. Histopathological examination revealed a seminomatous germ cell tumor (pT0, pN3, M0), clinical stage IIC, with a good prognosis. Therefore, chemotherapy was initiated with four cycles of EP (etoposide 170 mg and cisplatin 35 mg). However, despite standard chemotherapy, the disease progressed until the patient died. Conclusions: Cases of testicular tumor with retroperitoneal metastasis are rare and infrequently present with clinical, testicular, and imaging findings. Therefore, histopathology, accompanied by the intentional identification of mutations associated with the TP53 gene when therapeutic failure exists. Full article

Background/Objectives: Cancer is a chronic and heterogeneous disease, possessing molecular variation within a single type, resulting in its molecular subtypes. Cancer molecular subtyping offers biological insights into cancer variability, facilitating the development of personalized medicines. Various models have been proposed for cancer molecular subtyping, utilizing the high-dimensional transcriptomic, genomic, or proteomic data. The issue of data scarcity, characterized by high feature dimensionality and a limited sample size, remains a persistent problem.The objective of this research is to propose a deep learning framework, DeepCMS, that leverages the capabilities of feed-forward neural networks, gene set enrichment analysis, and feature selection to construct a well-representative subset of the feature space, thereby producing promising results. Methods: The gene expression data were transformed into enrichment scores, resulting in over 22,000 features. From those, the top 2000 features were selected, and deep learning was applied to these features. The encouraging outcomes indicate the efficacy of the proposed framework in terms of defining a well-representative feature space and accurately classifying cancer molecular subtypes. Results: DeepCMS consistently outperformed state-of-the-art models in aggregated accuracy, sensitivity, specificity, and balanced accuracy. The aggregated metrics surpassed 0.90 for all efficiency measures on independent test datasets, showing the generalizability and robustness of our framework. Although developed using colon cancer’s gene expression data, this approach may be applied to any gene expression data; a case study is also devised for illustration. Conclusions: Overall, the proposed DeepCMS framework enables the accurate and robust classification of cancer molecular subtypes using a compact and informative feature set, facilitating improved precision in oncology applications. Full article

Background: Seminoma is a malignant germ cell tumor that most commonly involves the testicles but may involve the mediastinum, the retroperitoneum, and other extra-gonadal sites as well. This study aims to investigate the somatic genomic landscape of seminoma. Methods: Data for a retrospective observational analysis of seminoma was acquired from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) with clinical and genomic data from 2017 and beyond. Using the R and R Studio software (R 4.5.0), analyses for common somatic mutations and copy number alterations were run with a statistical significance of p < 0.05. Results: The most mutated genes included KIT (22.6%), KRAS (17.1%), and MTOR (5.1%), with significant copy number alterations in CDKN1B (17.2%), KRAS (14.7%), CCND2 (10.3%), and H3F3C (9.8%). These suggest involvement within the KIT/RAS/MAPK and PI3K/AKT/mTOR (PAM) pathways for seminoma development. A novel finding within comparative evaluation of PMS1 and AMER1 mutations were found in Black individuals. Additionally, our findings were consistent with a lower testicular cancer rate among individuals with African ancestry than European ancestry. BRD4 mutations were found only in metastatic samples while KMT2C, STAG2, ALK, AXL, and EGFR were only found in primary samples, suggesting a possible association. Conclusions: This study provided a comprehensive molecular and genetic profiling of seminoma including key genetic alterations, affected pathways, and potential therapeutic strategies. Moreover, overlap between pathways and gene mutations provides the potential for alternative treatment options for seminoma via multiple pathways. Full article

Background/Objectives: Germ Cell Neoplasia In Situ (GCNIS) is considered the precursor lesion for the majority of testicular germ cell tumors (TGCTs). The aim of this study was to evaluate whether first-order radiomics features derived from volumetric diffusion tensor imaging (DTI) metrics—specifically apparent diffusion coefficient (ADC) and fractional anisotropy (FA) histogram parameters—can detect GCNIS. Methods: This study included 15 men with TGCTs and 10 controls. All participants underwent scrotal MRI, including DTI. Volumetric ADC and FA histogram metrics were calculated for the following tissues: group 1, TGCT; group 2: testicular parenchyma adjacent to tumor, histologically positive for GCNIS; and group 3, normal testis. Non-parametric statistics were used to assess differences in ADC and FA histogram parameters among the three groups. Pearson’s correlation analysis was followed by ordinal regression analysis to identify key predictive histogram parameters. Results: Widespread distributional differences (p < 0.05) were observed for many ADC and FA variables, with both TGCTs and GCNIS showing significant divergence from normal testes. Among the ADC statistics, the 10th percentile and skewness (p = 0.042), range (p = 0.023), interquartile range (p = 0.021), total energy (p = 0.033), entropy and kurtosis (p = 0.027) proved the most significant predictors for tissue classification. FA_energy (p = 0.039) was the most significant fingerprint of the carcinogenesis among the FA metrics. These parameters correctly characterized 88.8% of TGCTs, 87.5% of GCNIS tissues and 100% of normal testes. Conclusion: Radiomics features derived from volumetric ADC and FA histograms have promising potential to differentiate TGCTs, GCNIS, and normal testicular tissue, aiding early detection and characterization of pre-cancerous lesions. Full article

Fibrous sheath interacting proteins 1 and 2 (FSIP1 and FSIP2) are evolutionarily conserved testis-specific antigens, exclusively expressed in germ cells of adult human tissues, where they play essential roles in spermatogenesis and testicular development. Aberrant re-expression of FSIP1 and FSIP2, however, has been frequently reported in multiple malignancies, driving oncogenic processes including uncontrolled proliferation, invasion, migration, and metastasis, and correlating with unfavorable clinical outcomes. Their restricted expression in normal tissues, together with their consistent association with poor prognosis across cancer types, highlights their potential as diagnostic biomarkers, therapeutic targets, and prognostic indicators. This review summarizes the structural features and biological functions of the FSIP family, emphasizes recent advances in elucidating their regulatory roles in tumor-associated signaling pathways, and outlines the major challenges and future perspectives in this emerging field. Full article

Molecular profiling of testicular germ cell tumors (TGCTs) provides critical insights into personalized treatment approaches, particularly for patients with recurrent or treatment-resistant disease. In this study, we retrospectively analyzed clinicopathological and targeted genomic sequencing data from 27 TGCT patients, including 7 seminomas, 19 non-seminomas, and 1 prepubertal type teratoma, across stage I (48%), stage II (41%), and stage III (11%). Tumor samples were obtained from 27 orchiectomies, with additional pathological specimens collected from 16 of these patients during retroperitoneal lymph node dissections (RPLNDs); these included 8 chemotherapy-naïve and 8 post-chemotherapy cases. The median tumor mutational burden (TMB) was 0.5 mutations/Mb, consistent with the low mutation rate typically observed in TGCTs. Somatic mutations and copy number gain alterations were detected in 56% (15/27) of patients, primarily in KRAS (25.9%), KIT (11.1%), and PIK3CB (7.4%). PD-L1 positive immunoreactivity by immunohistochemistry was observed in 75% of tumors (60% in stage I, 100% in stage III) analyzed (n = 8), suggesting potential immune checkpoint inhibitor applicability in advanced disease. Microsatellite instability (MSI) status was identified in 23 tumors; all were classified as MSI-low, supporting the rarity of MSI-driven tumorigenesis in TGCTs. Actionable gene alterations linked to FDA-approved therapies, interventional therapies, and clinical trials in TGCTs and other cancers (lung, skin, colon, liver, stomach, and breast) were present in 59.3% (16/27) of patients, indicating potential therapeutic repurposing. Additionally, germline variants of uncertain clinical significance in known cancer actionable genes, including MSH2, MSH6, RB1, and BRCA2, were found in 9 patients, warranting further investigation regarding their clinical relevance and susceptibility risk. Our findings highlight that a substantial proportion of TGCT patients harbor potentially actionable molecular alterations across all disease stages. Full article

This study aims to investigate the molecular mechanisms underlying germ cell tumors (GCTs), focusing specifically on seminomas and teratomas. By analyzing gene expression profiles and miRNA interactions, the goal is to identify key regulatory miRNAs and signaling pathways that differentiate these tumor types and could serve as important regulators for therapy development. Raw data for seminomas and teratomas were extracted from the GEO database, and gene hubs were identified using STRING and Gephi. Signaling pathways and functional annotations were analyzed using miRPathDB, while miRNA–gene interactions were explored via miRWalk. Hub miRNAs were filtered and confirmed using miRDB. This study highlights significant changes in gene expression diversity between tumor and normal gonadal tissues, providing insights into the molecular dynamics of seminomas and teratomas. Distinctions between seminomas and teratomas were identified, shifting the focus toward miRNAs to discover more precise and novel therapeutic approaches. The hub genes of seminomas and teratomas were identified separately. MiRNAs targeting these hub genes were also determined and confirmed. These miRNAs collectively influence essential oncogenic pathways—confirming hsa-miR-138-5p as a regulator of pathways such as Hippo signaling, transcriptional misregulation in cancer, and microRNA cancer signaling in seminomas, and hsa-miR-200b-3p as a regulator of p53 signaling, T cell receptor signaling, and pathways including PI3K/AKT, MAPK/ERK, and Wnt/β-catenin in teratomas—confirming their potential as promising candidates for subtype-specific therapeutic intervention. MiRNAs identified through bioinformatics analyses, and their predicted regulatory roles in key oncogenic pathways, represent potential therapeutic targets or regulators of biological processes. However, further experimental validation is needed to confirm these findings. Full article

Background: Seminoma is the most common subtype of testicular germ cell tumors in young men; however, the contribution of tumor-associated macrophages (TAMs) to disease progression remains insufficiently understood. This study aimed to quantitatively and phenotypically characterize CD68⁺ and CD163⁺ TAMs in non-metastatic seminomas (pT1N0M0 and pT2N0M0). Methods: This retrospective, multicenter, cohort, observational, analytical study was conducted from 1 January 2015 to 1 January 2025 at two branches of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation: the A. Tsyb Medical Radiological Research Center and the P. Hertsen Moscow Oncology Research Institute. Archived paraffin-embedded tumor samples from 96 patients and 21 samples of normal testicular tissue were analyzed using immunohistochemistry and digital morphometric analysis with QuPath software to assess macrophage density and spatial distribution. Results: Compared to normal testicular tissue, seminomas demonstrated more than a 10-fold increase in CD68⁺ TAMs and over a 100-fold increase in CD163⁺ TAMs. CD68⁺ cells predominantly localized to peripheral tumor regions, while CD163⁺ cells formed diffuse clusters in central tumor zones and around peripheral vessels. No statistically significant differences in CD68⁺ cell density were found between pT1 and pT2 stages. However, pT2 tumors showed a trend toward higher CD163⁺ TAMs density, suggesting increased M2 polarization with advancing tumor stage. Conclusions: These findings highlight the spatial and phenotypic heterogeneity of TAMs in seminoma and indicate a shift toward an immunosuppressive tumor microenvironment during local progression. Future studies should assess macrophage polarization and progression-free survival to evaluate their potential as prognostic biomarkers and therapeutic targets in seminoma. Full article

Testicular germ cell tumors (TGCTs) are the most common malignancies affecting young men between the ages of 14 and 44, accounting for about 95% of all testicular cancers. Despite being relatively rare compared to other cancers (~3.0 cases per 100,000 population, with high worldwide variability), TGCTs’ incidence is increasing, particularly in industrialized countries. The initial phase of TGCT diagnosis is performed by detecting in the blood the presence of three proteins, i.e., alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), and human chorionic gonadotropin (hCG). Despite these proteins being defined as markers of TGCTs, they present limitations in specificity. Indeed, AFP is not elevated in pure seminomas; LDH serum levels can be elevated in other conditions, such as liver disease or tissue damage, and hCG can be elevated in both seminomas and non-seminomas, reducing its ability to differentiate between tumor types. However, the existence of hCG variants, characterized by distinct glycosylation profiles that are differentially expressed in TGCT types and subtypes, may increase the diagnostic and prognostic potential of this hormone. Furthermore, emerging molecular biomarkers, including miRNAs and tumor cells-related epigenetic status, may offer new promising alternatives to improve diagnostic accuracy. Nonetheless, standardized diagnostic protocols still need to be implemented. Finally, understanding the biological roles of hCG isoforms and their “canonical” (e.g., LHCGR) and “non-canonical” (e.g., TGF-βR) receptor interactions may help in understanding tumor biology and therapeutic targeting. Full article

Background/Objectives: Germ cell tumors are the most common neoplasia in males < 50 y. In two case series, thromboembolic events (TEs) were reported in 8% and 13% of patients undergoing chemotherapy, whereas arterial thromboembolic events (ATEs) in other types of cancer treated with cisplatin had a frequency of 2% in a retrospective series and 0.67% in a meta-analysis. Recent data found a frequency of 2.4% for ATE in a large cohort of testicular cancer patients. Risk factors are not clearly identified, and given the severity of these events, further exploration is needed to determine appropriate preventive measures. Methods: We performed a retrospective cohort study of 171 patients undergoing chemotherapy for germ cell tumors in two centers in Switzerland and recorded the occurrence of ATE or venous thromboembolic events (VTEs) during chemotherapy or in the 3 months after its completion. Results: of 171 patients, 33.3% underwent adjuvant chemotherapy for stage I disease. Overall, 32 patients had a TE (18.7%, 95% CI 13.3–25.5%), 26 (15.2%, 95% CI 10.3–21.7%) had VTEs, and 11 (6.4%, 95% CI 3.4–11.5%) had ATEs. Five patients had both a VTE and ATE. VTEs were associated with disease stage (II, III, or relapse, with OR 15.6, p = 0.0002), retroperitoneal lymph nodes ≥ 3.5 cm (OR 3.2, p = 0.012), LDH > 500 UI/L (OR 5.3, p = 0.0025), and age > 35 y (OR 3.4, p = 0.005). The Khorana Score (KS) varied between 1 and 2 in 96% of the patients. ATEs were associated with active smoking (OR 6.5 p = 0.010), KS of ≥2 (OR 6.4 p = 0.004), and age > 35 y (OR 6.3, p = 0.01). Conclusions: Our findings show that ATEs are more frequent in our cohort than previous reports. We found a strong association between smoking and ATEs, which should be further assessed. Platinum-induced endothelial damage may be amplified by smoking in young patients in the absence of other risk factors and preventive medication. Full article