Search Results (24)

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

Background/Objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors. This study aimed to assess the potential of differentially expressed miRNAs in differential diagnosis and prognostication among TGCT patients with various histologic subtypes. Methods: Transcriptomic analysis of 134 patients from The Cancer Genome Atlas (TCGA)-TGCT database was conducted. miRNA differential expression analysis among seminomatous, embryonal carcinoma, mixed GCT, and teratoma was performed, followed by ROC curve analysis of the most significantly up- and downregulated miRNAs, respectively. Statistical associations of miRNA expression with AJCC stage were also investigated along with miRNA target network analysis and evaluation of miRNA detection in patients’ fluids. Results: Upregulation of seven miRNAs (hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-200a, hsa-mir-200b, hsa-mir-203b, hsa-mir-375, hsa-mir-582) and downregulation of seven additional miRNAs (hsa-mir-105-1, hsa-mir-105-2, hsa-mir-4433a, hsa-mir-548x, hsa-mir-5708, hsa-mir-6715a, hsa-mir-767) were identified. miRNAs displayed a high sensitivity/specificity of 0.94/1.0 (AUC = 0.98) for the upregulated and 0.97/0.94 (AUC = 0.96) for the downregulated signature. Deregulated expression of these miRNAs was significantly associated with AJCC stage and distant organ metastasis (p < 0.001), overall supporting their prognostic strength. Both signatures were detectable in body fluids, particularly urine. miRNA target network analysis supported the functional role of these miRNAs in the regulation of cancer-related processes such as cell proliferation via deregulation of pivotal oncogenes. Conclusions: These findings support the clinical value of two novel miRNA signatures in differential diagnosis and prognostic stratification of various histologic subtypes of TGCT, with potential treatment implications. Full article

Testicular cancer is the most common cancer among young adult men and has favorable outcomes, with survival rates approaching 99% and over 80% for those with early and advanced stage disease, respectively. Biomarkers play a critical role in the diagnosis, pre-treatment risk stratification, surveillance, and assessment of post-treatment disease response in these men. Traditional serum tumor markers (STMs), which include alpha fetoprotein (AFP), beta subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are limited by low sensitivity (approximately 50%) during initial diagnosis; false-positive elevations as a result of other benign and malignant conditions; and negative levels in low-stage disease and in certain histologies such as teratoma and seminoma. As a result, novel biomarkers with potentially better performance characteristics, including microRNA (miRNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs), are being investigated. MicroRNAs are small noncoding RNA involved in transcription and translation and regulate the expression of almost one-third of human genes that regulate the cell cycle, differentiation, proliferation, and apoptosis. In germ cell tumor (GCT) patients, miR371a-3p has been identified as a promising biomarker with sensitivity and specificity of approximately 90–92% and 84–86%, respectively. The use of this new biomarker could aid in several clinical scenarios, such as predicting the presence of micrometastases in chemotherapy-naïve patients with clinical stage I–II disease, thereby guiding decisions on treatment versus surveillance and predicting the presence of viable GCT in patients with residual disease post chemotherapy. Clinical trials are ongoing to validate the use of miRNA 371 as a biomarker and to define its performance characteristics. Though promising, miRNAs are limited by their inability to detect teratoma. ctDNA and CTCs are two other emerging biomarkers, though further studies are needed to clarify their role in managing patients with GCT. Full article

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. Full article

Background: In staging for testicular germ cell tumor (GCT), current guidelines lack consensus regarding the measurement of retroperitoneal lymph node metastasis, concerning the recommended plane and dimension. This exploratory study aimed to assess its impact on clinical stage (cS) and therapy. Methods: We retrospectively examined 154 cSI (retroperitoneal lymph nodes < 10 mm in axial short-axis diameter (SAD)) GCT patients, without adjuvant therapy and a follow-up ≥ 24 months. Retroperitoneal lymph nodes were measured in staging images in different dimensions (SAD and long-axis diameter (LAD)) and planes (axial, sagittal and coronal). Results: Overall survival was 100%, with 82% free of recurrence after a median follow-up of 83 months. All patients were classified as cSI, based on axial SAD (RECIST 1.1). However, significantly more patients would have been classified as cSIIA (0% vs. 38% vs. 52%) or even cSIIB (0% vs. 1% vs. 25%) according to axial LAD (SWENOTECA, German S3 guideline) or maximum LAD in any plane (EAU, ESMO, AJCC and onkopedia) (p < 0.001). Overtreatment was predicted in 0%, 31% and 61% of patients based on axial SAD, axial LAD and maximum LAD, while undertreatment was estimated at 18%, 10% and 2%, respectively, (p < 0.001). Conclusions: These findings indicate considerable variability in cS based on current lymph node staging recommendations, suggesting that axial SAD (RECIST 1.1) could be the most appropriate parameter for standardized guideline recommendations. Full article

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed^®, Web of Science™, and Scopus^®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: “miRNA”, “non-coding RNA”, “small RNA”, “Testicular Cancer”, “seminomatous testicular germ cell”, “non-seminomatous testicular germ cell”. Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90–99%) and sensitivity (84–89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools. Full article

In vitro spermatogenesis (IVS) has important applications including fertility preservation of prepubertal cancer patients; however, thus far, IVS has only been achieved using mouse models. To study the effects of growth factors on the maintenance of testicular tissue integrity, germ cell numbers, and potential induction of IVS using a porcine model, we cultured small testicular fragments (~2 mg) from 1-wk-old piglets under six different media conditions (DMEM + 10%KSR alone or supplemented with GDNF, bFGF, SCF, EGF, or a combination of all) for 8 weeks. Overall, tissues supplemented with GDNF and bFGF had the greatest seminiferous tubule integrity and least number of apoptotic cells. GDNF-supplemented tissues had the greatest number of gonocytes per tubule, followed by bFGF-supplemented tissues. There was evidence of gradual Sertoli cell maturation in all groups. Moreover, histological examination and the expression of c-KIT (a marker of differentiating spermatogonia and spermatocytes) and STRA8 (a marker of the pre/meiotic stage germ cells) confirmed the induction of IVS in all groups. However, GDNF- and bFGF-supplemented tissue cultures had greater numbers of seminiferous tubules with spermatocytes compared to other groups. In conclusion, overall, GDNF and bFGF supplementation better maintained the tissue integrity and gonocyte numbers and induced IVS in cultured testicular tissues. Full article

Testicular germ cell tumors (TGCTs) are the leading cause of cancer-related death in males between the ages of 20 and 40. In the advanced stages, the combination of cisplatin-based chemotherapy and surgical excision of the remaining tumor can cure many of these patients. Vascular procedures may be required during retroperitoneal lymph node dissection (RPLND) in order to achieve the complete excision of all residual retroperitoneal masses. Careful assessment of pre-operative imaging and the identification of patients who could benefit from additional procedures are important for minimizing peri- and postoperative complications. We report on a case of a 27-year-old patient with non-seminomatous TGCT, who successfully underwent post-chemotherapy RPLND with additional infrarenal inferior vena cava (IVC) and complete abdominal aorta replacement using synthetic grafts. Full article

Spermatocytic tumor (ST) is a very rare disease, accounting for approximately 1% of testicular cancers. Previously classified as spermatocytic seminoma, it is currently classified within the non-germ neoplasia in-situ-derived tumors and has different clinical-pathologic features when compared with other forms of germ cell tumors (GCTs). A web-based search of MEDLINE/PubMed library data was performed in order to identify pertinent articles. In the vast majority of cases, STs are diagnosed at stage I and carry a very good prognosis. The treatment of choice is orchiectomy alone. Nevertheless, there are two rare variants of STs having very aggressive behavior, namely anaplastic ST and ST with sarcomatous transformation, that are resistant to systemic treatments and their prognosis is very poor. We have summarized all the epidemiological, pathological and clinical features available in the literature regarding STs that have to be considered as a specific entity compared to other germ GCTs, including seminoma. With the aim of improving the knowledge of this rare disease, an international registry is required. Full article

Standard care for stage I testicular germ cell cancers (seminomatous—STC or non-seminomatous—NSTC) is orchiectomy followed by active surveillance, 1 or 2 cycles of adjuvant chemotherapy, surgery or radiotherapy. The decision on the adjuvant therapeutic approach is guided by the associated risk factors of the patient and the potential related toxicity of the treatment. Currently, there is no consensus regarding the optimal number of adjuvant chemotherapy cycles. Although in terms of overall survival, there is no proven inconsistency regarding the number of cycles of adjuvant chemotherapy, and the rate of relapse may vary. Full article

Background and Objectives: The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database. Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004–2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality. Results: Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%; p < 0.01) and stage II (0.5 vs. 3.4%, p < 0.01), but not in stage I (0.9 vs. 1.6%, p = 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71, p = 0.01) and stage II (hazard ratio 0.11, p < 0.01). Conclusions: Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival. Full article

We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens were identified within the Surveillance, Epidemiology, and End Results database (2004–2019). Kaplan–Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%, p < 0.001; stage II: 100 vs. 95.9%, p < 0.001; stage III: 66.8 vs. 77.8%, p = 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%; p < 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%; p = 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83; p < 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92; p = 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM. Full article

SH3 domain and tetrapeptide repeat 2 (SH3TC2) is a protein-encoding gene and has previously been described as a critical signaling hub for neurological disorders. Although increasing evidence supports a vital role of SH3TC2 in the tumorigenesis of various kinds of cancer, no systematic analysis of SH3TC2 is available. The function and mechanism of SH3TC2 in other cancers remain unknown. Thus, this study aimed to analyze SH3TC2 in various kinds of cancer to find its tumorigenic role in one or more specific cancers. In the current study, we analyzed the expression level and prognostic value of SH3TC2 in different tumors in the TCGA-GTEx pan-cancer dataset. Subsequently, the prognostic role and mechanism of SH3TC2 in colorectal cancer (CRC) were further explored via clinical samples and in vitro and in vivo experiments. We observed differential expression of SH3TC2 in colon adenocarcinoma (COAD), acute myeloid leukemia (LAML), READ (rectum adenocarcinoma), SKCM (skin cutaneous melanoma), and TGCT (testicular germ cell tumors). Subsequently, SH3TC2 showed a significant effect on the clinical stage and prognostic value in CRC, LAML, and SKCM. Moreover, we found in the TCGA database and seven GEO datasets that SH3TC2 was significantly highly expressed in tumor tissue. Through enrichment analysis of SH3TC2 and its co-expressed genes, we found that SH3TC2 may play a role in the MAPK signaling pathway. Correlation analysis indicated that SH3TC2 was significantly associated with multiple key factors in the MAPK signaling pathway. Additionally, higher expression of SH3TC2 was found in tumor tissue in our cohort including 40 CRC patients. Overexpression of SH3TC2 may imply poor prognosis. Knockdown of SH3TC2 significantly inhibited tumor invasion, migration, and proliferation. More importantly, knockdown of SH3TC2 inhibited tumor growth in a CRC mouse model. The study preliminarily conducted a pan-cancer study of SH3TC2 and further explored the mechanism of SH3TC2 in CRC. Our research revealed that higher expression of SH3TC2 may promote CRC progression and invasion via the MAPK signaling pathway. Full article

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. Full article

Whole-Body Magnetic Resonance Imaging (WB-MRI) is increasingly used for metastatic screening in oncology. This prospective single center study assesses the diagnostic value of WB-MRI including diffusion weighted imaging (DWI) and identifies the sufficient protocol for metastatic lymph node detection in patients with testicular germ cell cancer (TGCC). Forty-three patients underwent contrast enhanced thoraco-abdominopelvic CT (TAP-CT) and WB-MRI with DWI for metastatic lymph node screening. Two independent readers reviewed CTs and WB-MRIs. The diagnostic performance of different imaging protocols (CT, complete WB-MRI, T1W + DWI, T2W + DWI), the agreement between these protocols and the reference standard, the reproducibility of findings and the image quality (Signal and contrast to Noise Ratios, Likert scale) were studied. Reproducibility was very good regardless of both lesion locations (retroperitoneal vs distant lymph nodes, other lesions) and the reader. Diagnostic accuracy of MRI was ≥95% (regardless of the locations and imaging protocol); accuracy of CT was ≥93%. There was a strict overlap of 95% CIs associated with this accuracy between complete WB-MRI, T1W + DWI and T2W + DWI, regardless of the reader. Higher Likert score and SNR were observed for DWI, followed by T2W and T1W sequences. In conclusion, a fast WB-MRI protocol including T2W and DWI is a sufficient, accurate, non-irradiating alternative to TAP-CT for metastatic lymph node screening in TGCC. Full article