Search Results (34)

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

Background/Objectives: Metastatic testicular germ cell tumor (mGCT) is a highly curable disease with first-line cisplatin-based combination chemotherapy. This study aims to evaluate the clinicopathological characteristics and survival outcomes of patients with metastatic testicular cancer in a nationwide multicenter cohort. Methods: This multicenter retrospective cohort study included 316 male patients diagnosed with mGCT who were treated with first-line cisplatin-based chemotherapy across 10 institutions in Turkey between 2011 and 2024. Clinical and pathological data, including International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, treatment details, and survival outcomes, were analyzed. Results: The median age of the cohort was 28 years, and 76.3% of patients were diagnosed with non-seminoma. According to IGCCCG risk stratification, 53.2% had good-risk, 25.3% intermediate-risk, and 21.5% poor-risk disease. Median follow-up was 38.4 months. Among patients with seminoma, the 5-year overall survival (OS) rate was 100% in the good-risk group and 87.5% in the intermediate-risk group. In patients with non-seminoma, 5-year OS rates were 96.6%, 86.9%, and 65.1% in the good-, intermediate-, and poor-risk groups, respectively. Among 125 patients who received salvage treatment, high-dose chemotherapy (HDCT) significantly improved survival in the International Prognostic Factors Study Group (IPFSG) very high-risk group (3-year OS: 55.0% vs. 16.3% with conventional-dose chemotherapy (CDCT), p = 0.007). Conclusions: This study provides the first large-scale nationwide dataset on mGCT outcomes in Turkey, demonstrating overall survival rates comparable to international cohorts. The findings emphasize the importance of a multidisciplinary approach, adherence to treatment guidelines, and optimal surgical interventions in improving patient outcomes. Full article

Background: Testicular germ cell tumors (GCTs) are highly curable malignancies, particularly when diagnosed early. However, cardiac metastases are exceedingly rare—occurring in less than 1% of cases—and pose significant diagnostic and therapeutic challenges. Intracardiac involvement is exceptionally uncommon and typically necessitates a multidisciplinary approach for optimal management. Objective: To present a rare case of metastatic testicular GCT with intracardiac extension in a young male, underscoring the diagnostic complexity and therapeutic considerations of this unusual clinical scenario. Case Report: A 23-year-old male presented with diffuse abdominal pain, dyspnea, and a palpable right testicular mass. Imaging revealed a testicular tumor with metastases to the lungs, liver, retroperitoneal lymph nodes, and a large intracardiac mass extending from the inferior vena cava into the right atrium. Histopathology confirmed a mixed-germ cell tumor consisting of 75% seminoma, 20% embryonal carcinoma, and 5% teratoma. The patient underwent radical right orchiectomy followed by chemotherapy with the BEP regimen (bleomycin, etoposide, cisplatin). Cardiac magnetic resonance imaging confirmed the intracardiac mass, which significantly decreased in size after treatment. Serum tumor markers (AFP and β-hCG) also showed substantial post-treatment declines, corresponding with clinical improvement. Conclusions: This case highlights a rare presentation of metastatic testicular GCT with intracardiac involvement, emphasizing the importance of recognizing atypical metastases. Despite its complexity, the patient responded well to chemotherapy, reinforcing the effectiveness of current treatments. Long-term follow-up and a multidisciplinary approach are essential for monitoring recurrence and complications, contributing to the understanding of rare metastatic patterns and the need for further research. Full article

The anti-cancer potential of eugenol (EUG) is well recognized, whereas that of spermidine (SPD) is subject to dispute and requires further research. The anti-tumorigenic potential of wheat germ SPD (150 µM) and clove EUG (100 µM), alone, in combination as SPD+EUG (50 µM + 100 µM) and, as a supplement (SUPPL; 0.6 µM SPD + 50 µM EUG), was investigated on both metastatic SW620 and primary Caco-2 colorectal cancer (CRC) spheroids. Compared to untreated controls, all treatments significantly reduced the vitality and spheroid area, increased the necrotic area, and induced apoptosis on both cell-type spheroids after 96 h, with a reduced migration evident in 2D (two-dimensional) cultures after 48 h. The comparable anti-CRC effects of the SPD+EUG and the SUPPL reflected a wide-range dose efficacy of SPD and EUG. It is of note that SPD+EUG induced a synergistic effect on the increased caspase-3 expression and reduced the migration percentage in SW620. In more physiologically relevant intestinal equivalents (healthy enterocytes [NCM460], fibroblasts [L929], and monocytes [U937]) containing embedded SW620/Caco-2 spheroids, SPD+EUG administration significantly reduced the spheroid CEA marker and proliferation, whilst simultaneously increasing occludin, autophagy LC3-II expression, and monocyte differentiation, compared to the control models. Exogenous SPD, alone and in combination with EUG, displayed an anti-CRC potential on tumor growth and metastasis, and warrants further investigation. Full article

(1) Background: Testicular cancer, although accounting for only 0.5% to 1% of all solid male cancers, is the most common malignancy in males aged 15 to 35 years. Non-seminomatous germ cell tumors (NSGCT) represent nearly half of all testicular germ cell tumors and are associated with a more aggressive clinical course. Spinal metastases, while rare, pose significant challenges due to their potential to cause spinal cord compression, neurological deficits, and severe pain. This systematic review aims to evaluate prognosis and treatment approaches for spinal metastases in NSGCT, with a focus on multidisciplinary care and treatment outcomes. (2) Methods: A systematic review was conducted following PRISMA guidelines. PubMed, Scopus, and Embase were searched on 18 September 2024, using the Boolean search strategy [(Nonseminomatous germ cell tumor (NSGCT) AND (spinal OR vertebral metastases)]. Case reports, case series, and cohort studies providing detailed patient data were included. Data on patient demographics, tumor histology, metastatic site, treatments, and outcomes were extracted for analysis. (3) Results: A total of 164 cases of NSGCT with spinal metastases were analyzed, with patients aged 23 to 40 years (median: 31.5 years). The lumbar spine was involved in all cases, and spinal cord compression occurred in 59.8% of patients, often causing severe neurological symptoms such as cauda equina syndrome. Chemotherapy, primarily cisplatin-based, was administered in all cases, while surgical interventions, including laminectomy and vertebrectomy, were performed in cases of spinal compression and instability. Complete remission occurred in only 2.4% of patients. Progressive improvement was observed in 56.7% of cases, while 20.1% of patients died. Outcomes varied, highlighting the importance of individualized, multidisciplinary care to manage both systemic and localized disease. (4) Conclusions: Spinal metastases in NSGCT represent a complex clinical scenario, requiring a combination of chemotherapy, surgery, and in some cases, radiotherapy. Chemotherapy remains essential, but surgery is critical for addressing spinal compression and instability. A multidisciplinary approach is vital for optimizing outcomes, as prognosis is variable, with some patients achieving improvement while others face progressive disease or death. Further research is needed to refine the role of radiotherapy and improve long-term treatment strategies for this rare complication. Full article

Germ cell tumor of the testis (GCT) is a curable cancer even when it is widely metastatic; however, outcomes can differ based on tumor histology. Chemo-resistance in certain phenotypes, such as teratoma and yolk sac tumor, contributes to poor clinical outcomes in some patients with GCT. Despite this resistance to S-YSTemic therapy, many of these tumor subtypes remain amenable to surgical resection and possible cure. In this study, we report on a series of seven patients highlighting two chemo-resistant subtypes of nonseminomatous germ cell tumor (NSGCT), sarcomatoid yolk sac tumor (S-YST), and epithelioid trophoblastic tumor (ETT) for which early resection rather than additional salvage chemotherapy or high-dose intense chemotherapy might provide a superior clinical outcome and enhance cure rate. Full article

The Sertoli cells (SeCs) of the seminiferous tubules secrete a multitude of immunoregulatory and trophic factors to provide immune protection and assist in the orderly development of germ cells. Grafts of naked or encapsulated SeCs have been proved to represent an interesting therapeutic option in a plethora of experimental models of diseases. However, whether SeCs have immunosuppressive or immunomodulatory effects, which is imperative for their clinical translatability, has not been demonstrated. We directly assessed the immunopotential of intraperitoneally grafted microencapsulated porcine SeCs (MC-SeCs) in murine models of fungal infection (Aspergillus fumigatus or Candida albicans) or cancer (Lewis lung carcinoma/LLC or B16 melanoma cells). We found that MC-SeCs (i) provide antifungal resistance with minimum inflammatory pathology through the activation of the tolerogenic aryl hydrocarbon receptor/indoleamine 2,3-dioxygenase pathway; (ii) do not affect tumor growth in vivo; and (iii) reduce the LLC cell metastatic cancer spread associated with restricted Vegfr2 expression in primary tumors. Our results point to the fine immunoregulation of SeCs in the relative absence of overt immunosuppression in both infection and cancer conditions, providing additional support for the potential therapeutic use of SeC grafts in human patients. Full article

Background: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). Methods: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. Results: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. Conclusions: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP. Full article

Testicular germ cell tumors (TGCTs) are cancers with very good prognosis, even in the metastatic setting, with high curative potential mainly attributed to the introduction of cisplatin-based chemotherapy. However, approximately 15% of the patients develop platinum-refractory disease and suffer multiple relapses. Therefore, there is an unmet need for novel therapeutic agents with improved efficacy and minimal long-term side effects. Recent advances in the development of immunotherapeutic agents, particularly immune checkpoint inhibitors (ICIs), have offered an opportunity to test their activity in various tumor types, including GCTs. This review aims to analyze the immune microenvironment of these tumors and present the most recently available data from studies that have tested immunotherapeutic agents against GCTs. The majority of the available knowledge derives from case reports or small cohort studies, particularly those involving ICIs of the PD-1/PD-L1 axis alone or in combination with anti-CTLA-4 monoclonal antibodies. Other immunotherapeutic targeted approaches, including antibody-drug conjugates, antibody prodrugs, vaccines, tyrosine kinase inhibitors, chimeric antigen receptor (CAR) T-cell therapy, have biological rationales and have shown preliminary activity or are currently being tested. Growing evidence on these and other approaches will assist in broadening the currently limited treatment armamentarium against platinum-refractory TGCTs. Full article

The outcome of metastatic testicular germ cell tumor patients has been dramatically improved by cisplatin-based chemotherapy combinations. However, up to 30% of patients with advanced disease relapse after first-line therapy and require salvage regimens, which include treatments with conventional-dose chemotherapy or high-dose chemotherapy with autologous stem cell transplantation. For these patients, prognosis estimation represents an essential step in the choice of medical treatment but still remains a complex challenge. The available histological, clinical, and biochemical parameters attempt to define the prognosis, but they do not reflect the tumor’s molecular and pathological features and do not predict who will exhibit resistance to the several treatments. Molecular selection of patients and validated biomarkers are highly needed in order to improve current risk stratification and identify novel therapeutic approaches for patients with recurrent disease. Biomolecular biomarkers, including microRNAs, gene expression profiles, and immune-related biomarkers are currently under investigation in testicular germ cell tumors and could potentially hold a prominent place in the future treatment selection and prognostication of these tumors. The aim of this review is to summarize current scientific data regarding prognostic and predictive biomarkers for salvage therapy in testicular germ cell tumors. Full article

Background: The identification of histopathology in metastatic non-seminomatous testicular germ cell tumors (TGCT) before post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) holds significant potential to reduce treatment-related morbidity in young patients, addressing an important survivorship concern. Aim: To explore this possibility, we conducted a study investigating the role of computed tomography (CT) radiomics models that integrate clinical predictors, enabling personalized prediction of histopathology in metastatic non-seminomatous TGCT patients prior to PC-RPLND. In this retrospective study, we included a cohort of 122 patients. Methods: Using dedicated radiomics software, we segmented the targets and extracted quantitative features from the CT images. Subsequently, we employed feature selection techniques and developed radiomics-based machine learning models to predict histological subtypes. To ensure the robustness of our procedure, we implemented a 5-fold cross-validation approach. When evaluating the models’ performance, we measured metrics such as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, and F-score. Result: Our radiomics model based on the Support Vector Machine achieved an optimal average AUC of 0.945. Conclusions: The presented CT-based radiomics model can potentially serve as a non-invasive tool to predict histopathological outcomes, differentiating among fibrosis/necrosis, teratoma, and viable tumor in metastatic non-seminomatous TGCT before PC-RPLND. It has the potential to be considered a promising tool to mitigate the risk of over- or under-treatment in young patients, although multi-center validation is critical to confirm the clinical utility of the proposed radiomics workflow. Full article

Primary retroperitoneal carcinomas are very rare tumors. Their pathogenesis remains unknown but may be associated with that of ovarian carcinomas, considering the similarity in morphology and gender preference. Although metaplasia of coelomic epithelium is the most widely accepted theory, the pathogenesis of retroperitoneal carcinomas may differ by histologic subtype, like ovarian carcinomas. Mucinous carcinoma, which develops in both women and men, may originate in both primordial germ cells and Walthard cell nests that may be derived from the fallopian tube. Serous carcinomas may be associated with endosalpingiosis, the presence of fallopian tube-like epithelium outside the fallopian tube, and a remnant Müllerian tract. Endometrioid and clear cell carcinomas appear to be associated with extraovarian endometriosis. Additionally, both carcinomas in the retroperitoneal lymph nodes may be metastatic diseases from endometrial and/or renal cell cancer that regress spontaneously (carcinoma of unknown primary). Retroperitoneal carcinomas are difficult to diagnose, as they have no characteristic symptoms and signs. Surgery is the cornerstone of treatment, but the necessity of chemotherapy may depend on histological subtype. Further studies are necessary, in particular studies on endosalpingiosis, as endosalpingiosis is a poorly understood condition, although it is associated with the development of both serous and mucinous carcinomas. Full article

Background: Although metastatic germ cell tumor (GCT) is highly curable with initial cisplatin-based chemotherapy (CT), 20–30% of patients relapse. Salvage CT options include conventional (CDCT) and high dose chemotherapy (HDCT), however definitive comparative data remain lacking. We aimed to characterize the contemporary practice patterns of salvage CT across Canada. Methods: We conducted a 30-question online survey for Canadian medical and hematological oncologists with experience in treating GCT, assessing treatment availability, patient selection, and management strategies used for relapsed GCT patients. Results: There were 30 respondents from 18 cancer centers across eight provinces. The most common CDCT regimens used were TIP (64%) and VIP (25%). HDCT was available in 13 centers (70%). The HDCT regimen used included carboplatin and etoposide for two cycles (76% in 7 centers), three cycles (6% in 2 centers), and the TICE protocol (11%, in 2 centers). “Bridging” CDCT was used by 65% of respondents. Post-HDCT treatments considered include surgical resection for residual disease (87.5%), maintenance etoposide (6.3%), and surveillance only (6.3%). Conclusions: HDCT is the most commonly used GCT salvage strategy in Canada. Significant differences exist in the treatment availability, selection, and delivery of HDCT, highlighting the need for standardization of care for patients with relapsed testicular GCT. Full article

Background: Brachytherapy (BT) has a major role in pediatric cancers of the lower genital tract, as part of a multimodal organ conservative strategy. Scarce data are available on the location of image-guided BT. Methods: Medical records of all consecutive girls treated in our center between 2005 and 2020 for a vaginal tumor with exclusive image-guided PDR-BT were retrospectively examined, with a focus on treatment parameters, patient compliance, and clinical outcome, including analysis of local control, survival and late toxicity rates. Results: Twenty-six patients were identified, with a median age of 25 months. Histological types were rhabdomyosarcoma, malignant germ cell tumor (MGCT) and clear cell adenocarcinoma in 18 (69%), 7 (27%) and 1 (4%) patients, respectively. Ten (33%) patients had prior surgery and 25 (96%) received chemotherapy prior to BT. The median prescribed dose was 60 Gy through pulses of 0.42 Gy. Global compliance was satisfactory, but three (12%) patients required replanning because of applicator displacement. After a median follow-up of 47.5 months, one patient with MGCT referred for salvage treatment of a local recurrence had a local and metastatic relapse. The local control rate probability was 96% at the last follow-up. Late toxicity rates ≥ grade 2 and ≥ grade 3 were reported in 23% and 11%, respectively, with gynecological toxicities being the most frequent side effect. Two patients required dilatation for vaginal stenosis. Conclusions: PDR-BT allowed similar local control compared to the historical low-dose rate technique. An indirect comparison suggests fewer treatment-related toxicities by integrating image guidance and optimization capabilities, but longer follow-up is necessary. Due to the rarity of the disease and the technical aspects of BT in these very young patients, referral to specialized high-volume centers is recommended. 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