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European Urology Focus May 2024Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable...
BACKGROUND AND OBJECTIVE
Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment.
METHODS
A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test.
KEY FINDINGS AND LIMITATIONS
The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation.
CONCLUSIONS AND CLINICAL IMPLICATIONS
The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery.
PATIENT SUMMARY
The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.
PubMed: 38729824
DOI: 10.1016/j.euf.2024.05.002 -
Cureus Apr 2024Germ cell tumors are malignant tumors that mostly develop in the gonads. Extragonadal localization is rare and may affect the mediastinal and sacrococcygeal regions....
Germ cell tumors are malignant tumors that mostly develop in the gonads. Extragonadal localization is rare and may affect the mediastinal and sacrococcygeal regions. Mediastinal seminoma is a malignant germ cell tumor of the mediastinum. The tumor typically occurs in the anterosuperior mediastinum in males and often has a very slow growth pattern and limited potential for metastasis. And symptoms are not very characteristic, with many patients being asymptomatic and the tumor being discovered incidentally. In this paper, we report the case of a 26-year-old patient admitted for the management of a large anterosuperior mediastinal tumor encasing the vital structures of the mediastinum.
PubMed: 38707071
DOI: 10.7759/cureus.57504 -
International Braz J Urol : Official... 2024Chemotherapy and radiation therapy are considered standard treatments for stage II seminoma patients; however, these therapies are associated with long-term toxicities.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Chemotherapy and radiation therapy are considered standard treatments for stage II seminoma patients; however, these therapies are associated with long-term toxicities. Recently, retroperitoneal lymph node dissection has emerged as an alternative strategy, and the first three phase II trials were published in 2023 with promising results. The present study conducted a systematic review and meta-analysis to evaluate this surgery as an alternative treatment for stage IIA/B seminoma patients.
PURPOSE
Seminomas are the most common testicular tumors, often affecting young adult males. Standard treatments for stage II seminomas include chemotherapy and radiation therapy, but these therapies are associated with long-term toxicities. Thus, identifying alternative strategies is paramount. Herein, we conducted a systematic review and meta-analysis to appraise the efficacy and safety of retroperitoneal lymph node dissection (RPLND) for treating this condition.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases for studies evaluating RPLND as a primary treatment for stage II A/B seminomas. Using a random-effects model, single proportion and means and pooled 2-year recurrence-free survival rates with hazard rates and 95% CI were calculated.
RESULTS
Seven studies were included, comprising 331 males with stage II seminomas. In the pooled analysis, the recurrence rate was 17.69% (95% CI 12.31-24.75), and the 2-year RFS rate was 81% (95% CI 0.77-0.86). The complication rate was 9.16% (95% CI 6.16-13.42), the Clavien-Dindo > 2 complication rate was 8.83% (95% CI 5.76-13.31), and the retrograde ejaculation rate was 7.01% (95% CI 3.54-13.40). The median operative time was 174.68 min (95% CI 122.17-249.76 min), median blood loss was 105.91 mL (95% CI 46.89-239.22 mL), and patients with no evidence of lymph node involvement ranged from 0-16%.
CONCLUSIONS
Primary RPLNDs for treating stage IIA/B seminomas have favorable RFS rates, with low complication and recurrence rates. These findings provide evidence that this surgery is a viable alternative therapy for these patients.
Topics: Humans; Lymph Node Excision; Seminoma; Testicular Neoplasms; Male; Neoplasm Staging; Retroperitoneal Space; Treatment Outcome; Disease-Free Survival
PubMed: 38701185
DOI: 10.1590/S1677-5538.IBJU.2024.0134 -
Stem Cell Research & Therapy May 2024Testicular germ cell tumours (TGCTs) represent a clinical challenge; they are most prevalent in young individuals and are triggered by molecular mechanisms that are not...
BACKGROUND
Testicular germ cell tumours (TGCTs) represent a clinical challenge; they are most prevalent in young individuals and are triggered by molecular mechanisms that are not fully understood. The origin of TGCTs can be traced back to primordial germ cells that fail to mature during embryonic development. These cells express high levels of pluripotency factors, including the transcription factor NANOG which is highly expressed in TGCTs. Gain or amplification of the NANOG locus is common in advanced tumours, suggesting a key role for this master regulator of pluripotency in TGCT stemness and malignancy.
METHODS
In this study, we analysed the expression of microRNAs (miRNAs) that are regulated by NANOG in TGCTs via integrated bioinformatic analyses of data from The Cancer Genome Atlas and NANOG chromatin immunoprecipitation in human embryonic stem cells. Through gain-of-function experiments, MIR9-2 was further investigated as a novel tumour suppressor regulated by NANOG. After transfection with MIR9-2 mimics, TGCT cells were analysed for cell proliferation, invasion, sensitivity to cisplatin, and gene expression signatures by RNA sequencing.
RESULTS
For the first time, we identified 86 miRNAs regulated by NANOG in TGCTs. Among these, 37 miRNAs were differentially expressed in NANOG-high tumours, and they clustered TGCTs according to their subtypes. Binding of NANOG within 2 kb upstream of the MIR9-2 locus was associated with a negative regulation. Low expression of MIR9-2 was associated with tumour progression and MIR9-2-5p was found to play a role in the control of tumour stemness. A gain of function of MIR9-2-5p was associated with reduced proliferation, invasion, and sensitivity to cisplatin in both embryonal carcinoma and seminoma tumours. MIR9-2-5p expression in TGCT cells significantly reduced the expression of genes regulating pluripotency and cell division, consistent with its functional effect on reducing cancer stemness.
CONCLUSIONS
This study provides new molecular insights into the role of NANOG as a key determinant of pluripotency in TGCTs through the regulation of MIR9-2-5p, a novel epigenetic modulator of cancer stemness. Our data also highlight the potential negative feedback mediated by MIR9-2-5p on NANOG expression, which could be exploited as a therapeutic strategy for the treatment of TGCTs.
Topics: Humans; Nanog Homeobox Protein; MicroRNAs; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms; Male; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Cell Proliferation; Neoplastic Stem Cells; Cisplatin
PubMed: 38693576
DOI: 10.1186/s13287-024-03724-1 -
Journal of Biotechnology Jun 2024Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of...
BACKGROUND
Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1 cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease.
OBJECTIVE
To assess patient outcomes and complications considering different treatment regimens and clinical characteristics.
MATERIALS AND METHODS
In a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed.
RESULTS
Standard 3-4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5-6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases.
CONCLUSIONS
The study suggests no significant benefit from exceeding 3-4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical.
Topics: Humans; Male; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Adult; Cross-Sectional Studies; Young Adult; Treatment Outcome; Lymph Node Excision; Middle Aged; Adolescent; Neoplasm, Residual; Orchiectomy; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy
PubMed: 38692356
DOI: 10.1016/j.jbiotec.2024.04.018 -
Medicina (Kaunas, Lithuania) Mar 2024The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing... (Review)
Review
The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.
Topics: Humans; Testicular Neoplasms; Male; Sexual Dysfunction, Physiological; Quality of Life; Sexuality; Erectile Dysfunction
PubMed: 38674232
DOI: 10.3390/medicina60040586 -
British Journal of Cancer Jun 2024Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T...
BACKGROUND
Immune cell infiltration is heterogeneous but common in testicular germ cell tumors (TGCT) and pre-invasive germ cell neoplasia in situ (GCNIS). Tumor-infiltrating T cells including regulatory T (Treg) and follicular helper T (Tfh) cells are found in other cancer entities, but their contributions to TGCT are unknown.
METHODS
Human testis specimens from independent patient cohorts were analyzed using immunohistochemistry, flow cytometry and single-cell RNA sequencing (scRNA-seq) with special emphasis on delineating T cell subtypes.
RESULTS
Profound changes in immune cell composition within TGCT, shifting from macrophages in normal testes to T cells plus B and dendritic cells in TGCT, were documented. In most samples (96%), the CD4+ T cell frequency exceeded that of CD8+ cells, with decreasing numbers from central to peripheral tumor areas, and to tumor-free, contralateral testes. T cells including Treg and Tfh were most abundant in seminoma compared to mixed tumors and embryonal carcinoma.
CONCLUSION
Despite considerable heterogeneity between patients, T cell subtypes form a key part of the TGCT microenvironment. The novel finding of rare Treg and Tfh cells in human testis suggests their involvement in TGCT pathobiology, with implications for understanding tumor progression, to assess patients' prognosis, and as putative targets for personalized immunotherapy.
Topics: Humans; Testicular Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; T-Lymphocytes, Regulatory; Tumor Microenvironment; Lymphocytes, Tumor-Infiltrating; CD8-Positive T-Lymphocytes; Single-Cell Analysis; Testis; Adult
PubMed: 38649788
DOI: 10.1038/s41416-024-02669-9 -
Radiology Case Reports Jul 2024Testicular seminoma commonly occurs in young men aged between 15 and 45 years old. Those with testicular cancer may present with a lump or swelling in the testicle. If...
Testicular seminoma commonly occurs in young men aged between 15 and 45 years old. Those with testicular cancer may present with a lump or swelling in the testicle. If treated and managed early, patients can expect a greater than 95% success rate. However, advanced stages of testicular seminoma can lead to eventual metastasis. We present a 45-year-old male patient with a prior history of testicular seminoma who was admitted to the emergency department with abdominal distension and acute abdominal pain. The CT identified a rather sizable abdominal mass and the biopsy confirmed metastatic testicular seminoma. Lymphoma was considered as the other differential diagnosis. Abdominal metastasis is rare in patients with testicular seminoma and usually leads to a poor survival outcome. Our patient did not attend follow-up appointments postorchidectomy, likely resulting in abdominal metastasis of testicular seminoma. This demonstrates the importance of ongoing surveillance of seminoma patients, and the challenges associated with differentiating large abdominal conglomerate mass in the CT scan. This patient is currently on active chemotherapy with bleomycin, cisplatin, and etoposide.
PubMed: 38645951
DOI: 10.1016/j.radcr.2024.03.012 -
Cureus Mar 2024Rhabdomyosarcoma (RMS) is a highly sporadic, very aggressive, and fatal soft tissue tumor in adults. Although more common and treatable in the pediatric population, the...
Rhabdomyosarcoma (RMS) is a highly sporadic, very aggressive, and fatal soft tissue tumor in adults. Although more common and treatable in the pediatric population, the occurrence of pleomorphic RMS in adults has a low incidence. Hence, it is not easy to treat. Surgery is the primary definitive treatment, along with radiation therapy, while adjuvant chemotherapy has recently gained popularity. We present an infrequent case of RMS in a patient with a recent history of mixed non-seminomatous germ-cell tumor testicular cancer. Therefore, it was challenging to treat the RMS as a new malignancy or as a recurrence of non-seminomatous testicular cancer. Our patient passed away, unfortunately, but we hope this case can help the minimal data in this regard in order to save more lives in the future.
PubMed: 38571873
DOI: 10.7759/cureus.55449 -
Journal of Clinical Medicine Mar 2024Preferentially expressed antigen in melanoma (PRAME), a member of the cancer testis antigen family, is a promising target for cancer immunotherapy. Understanding the...
Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes.
Preferentially expressed antigen in melanoma (PRAME), a member of the cancer testis antigen family, is a promising target for cancer immunotherapy. Understanding the epigenetic mechanisms involved in the regulation of PRAME expression might be crucial for optimizing anti-PRAME treatments. Three malignancies of different lineages (sinonasal melanoma, testicular seminoma, and synovial sarcoma), in which immunohistochemical (IHC) reactivity for PRAME is a common yet variable feature, were studied. The expression of PRAME, ten-eleven translocation demethylase 1 (TET1), and DNA methyltransferase (DNMT) 3A and 3B were evaluated using immunohistochemistry. Moreover, the expression of two epigenetic marks, 5-hydroxymethylcytosine (5hmC) and histone 3 acetylation (H3ac), was tested. All PRAME-positive tumors expressed medium-to-high levels of H3ac but differed considerably with respect to other markers. In seminomas, PRAME expression correlated with TET1, but in melanomas and synovial sarcomas, it correlated with both DNMTs and DNMT3A, respectively. PRAME expression was not determined by a balance between the global expression of DNA methylating/demethylating enzymes. However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.
PubMed: 38541782
DOI: 10.3390/jcm13061554