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1.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361047

RESUMO

Chemoresistance of germ cell tumors (GCTs) represents an intensively studied property of GCTs that is the result of a complicated multifactorial process. One of the driving factors in this process is the tumor microenvironment (TME). Intensive crosstalk between the DNA damage/DNA repair pathways and the TME has already been reported. This study aimed at evaluating the interplay between the immune TME and endogenous DNA damage levels in GCT patients. A cocultivation system consisting of peripheral blood mononuclear cells (PBMCs) from healthy donors and GCT cell lines was used in an in vitro study. The patient cohort included 74 chemotherapy-naïve GCT patients. Endogenous DNA damage levels were measured by comet assay. Immunophenotyping of leukocyte subpopulations was performed using flow cytometry. Statistical analysis included data assessing immunophenotypes, DNA damage levels and clinicopathological characteristics of enrolled patients. The DNA damage level in PBMCs cocultivated with cisplatin (CDDP)-resistant GCT cell lines was significantly higher than in PBMCs cocultivated with their sensitive counterparts. In GCT patients, endogenous DNA damage levels above the cutoff value were independently associated with increased percentages of natural killer cells, CD16-positive dendritic cells and regulatory T cells. The crosstalk between the endogenous DNA damage level and specific changes in the immune TME reflected in the blood of GCT patients was revealed. The obtained data contribute to a deeper understanding of ongoing interactions in the TME of GCTs.


Assuntos
Dano ao DNA , Leucócitos Mononucleares/imunologia , Neoplasias Testiculares/imunologia , Microambiente Tumoral/imunologia , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/imunologia , Linhagem Celular Tumoral , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucócitos Mononucleares/classificação , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia
2.
Pan Afr Med J ; 39: 71, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34422194

RESUMO

We here report a case of embryonal paratesticular rhabdomyosarcoma in a young adult. The purpose of this study is to highlight this uncommon histological type of tumor in this age group, the rapid evolution of the lesion and the challenges of managing it in our context.


Assuntos
Rabdomiossarcoma Embrionário/diagnóstico , Neoplasias Testiculares/diagnóstico , Humanos , Masculino , Rabdomiossarcoma Embrionário/patologia , Neoplasias Testiculares/patologia , Adulto Jovem
4.
Am J Surg Pathol ; 45(10): 1303-1313, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232606

RESUMO

Sex cord-stromal tumors (SCSTs) account for the second most common category of testicular neoplasms and include several entities that may show overlapping morphologies and present diagnostic challenges. We analyzed a cohort of 120 testicular SCSTs and investigated the diagnostic utility of SRY-box transcription factor 9 (SOX9), forkhead box protein L2 (FOXL2), and steroidogenic factor 1 (SF-1) immunohistochemical stains. The results were compared with the more commonly used SCST markers, inhibin α, calretinin, and Wilms' tumor 1 (WT1). SF-1 was overall the most sensitive stain (91%), followed by inhibin α (70%), calretinin (52%), FOXL2 (50%), SOX9 (47%), and WT1 (37%), but sensitivities varied by tumor type. SOX9 and calretinin were more commonly positive in sex cord elements versus stromal elements (62% vs. 27% and 47% vs. 9%, respectively), whereas FOXL2 was more commonly positive in stromal elements versus sex cord elements (100% vs. 55%) when excluding Leydig cell tumors from the stromal category. Although no individual stain was diagnostically specific, some immunophenotypic patterns were noted that may help in the subclassification of SCSTs. We conclude that SOX9, FOXL2, and SF-1 are useful immunohistochemical stains for confirming sex cord-stromal differentiation in testicular tumors and provide increased sensitivity as well as additional diagnostic information, especially when combined with the more commonly used inhibin α, calretinin, and WT1 immunostains. Although morphology is paramount for subclassification of SCSTs, knowledge of certain immunohistochemical patterns may be helpful for diagnostically challenging cases.


Assuntos
Biomarcadores Tumorais/análise , Proteína Forkhead Box L2/análise , Imuno-Histoquímica , Fatores de Transcrição SOX9/análise , Tumores do Estroma Gonadal e dos Cordões Sexuais/química , Fator Esteroidogênico 1/análise , Neoplasias Testiculares/química , Animais , Calbindina 2/análise , Humanos , Inibinas/análise , Masculino , Valor Preditivo dos Testes , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Neoplasias Testiculares/patologia , Proteínas WT1/análise
5.
Int J Mol Sci ; 22(11)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34205983

RESUMO

In the human embryo, the genetic program that orchestrates germ cell specification involves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neoplasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types.


Assuntos
Neoplasias Embrionárias de Células Germinativas/genética , Teratoma/genética , Neoplasias Testiculares/genética , Transcrição Genética , Diferenciação Celular/genética , Epigenômica , Células Germinativas/crescimento & desenvolvimento , Células Germinativas/patologia , Gônadas/crescimento & desenvolvimento , Gônadas/patologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Células-Tronco Pluripotentes/citologia , Teratoma/patologia , Neoplasias Testiculares/patologia
6.
Urologe A ; 60(7): 847-853, 2021 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-34232324

RESUMO

Testicular cancer occupies a special position in several respects. Although it belongs to the group of rare tumors, which is why extensive experience in treating this tumor can not be guaranteed, interdisciplinary experts collaboration and the consequent implementation of clinical studies have resulted in standardized treatment recommendations. Because testicular cancer is one of the most curable cancers, long-term toxicity and treatment sequelae are of special importance. In the early stages, toxicity could be reduced by minimizing therapy to the extent possible, but without decreasing treatment success. Nevertheless, treatment is still controversially discussed, especially concerning treatment of stage I disease. Finally particular focus should be paid to non-germinal tumors which are even more rare, but partly also more dangerous. Therefore known facts should be made available for the broad medical community. In penile cancer, which is also a very rare tumor entity, organ-sparing surgery and consequent invasive lymph node staging are mandatory.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Penianas , Neoplasias Testiculares , Humanos , Excisão de Linfonodo , Masculino , Estadiamento de Neoplasias , Neoplasias Penianas/patologia , Qualidade de Vida , Encaminhamento e Consulta , Neoplasias Testiculares/patologia
7.
Arch Esp Urol ; 74(4): 397-403, 2021 May.
Artigo em Espanhol | MEDLINE | ID: mdl-33942732

RESUMO

INTRODUCTION: The active surveillance (AS) of testicular tumors (seminoma and non-seminoma) is the most frequent management option in the stage I disease. Relapses generally occurred within the first 3 years and <5% appear after this time cut-off point is fulfilled. Therefore, the adherence is one of the most important pillars in the AS protocol. The aim of this study is to evaluate the adherence to the AS protocol in a community hospital and, in turn, evaluate the safety of it emphasizing in the relapse-free rate in patients with and without risk factors. MATERIALS AND METHODS: A retrospective study of all the patients included in the AS protocol with seminoma tumors (ST) or non-seminoma tumors (NST) stage I was performed. Postoperative controls were performed according to the NCCN (National Comprehensive Cancer Network) recommendations. Different variables were taken into account, emphasizing in the risk factors: testicular tumor >4cm and the rete testis invasion in the ST, the linfovascular invasion and the percentage>40% of embrionary carcinoma in the NST. Adherence to the AS protocol was evaluated, focusing on those patients who lost it and what time it occurred. RESULTS: A total of 64 patients were included. The median follow-up was 36 months (IC 21-48 months). 12 patients lost the follow-up during the protocol with a median follow-up of 27.5 months (IC 16-30 months). A 21.8% of patients entered in the AS protocol with some associated risk factor. Adherence follow-up was successful in the first year (96.8%) and decreased over time (92.2% at 24 months and 86.3% at 36 months). CONCLUSION: We presented an important adherence to the AS protocol in patients with clinical stage I testicular cancer and in our series there no recurrences after 36 months of follow-up.


Assuntos
Neoplasias Testiculares , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Conduta Expectante
8.
J Clin Oncol ; 39(14): 1563-1574, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33822655

RESUMO

PURPOSE: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. MATERIALS AND METHODS: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. RESULTS: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). CONCLUSION: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Humanos , Cooperação Internacional , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto Jovem
9.
Adv Anat Pathol ; 28(4): 258-275, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33871428

RESUMO

Testicular tumors are incredibly diverse and one of the most challenging areas in surgical pathology. Because of the rarity and overlapping features with numerous entities occurring in the testis and paratestis, these tumors pose a diagnostic challenge even to the most experienced general pathologists. In 2016, the latest "World Health Organization (WHO) classification of testicular tumors" was released, which incorporated several updates to the previous 2004 classification system. These updates involved several entities, including germ cell tumors, sex cord-stromal tumors, tumors containing both germ cells and sex-cord stromal cells, a miscellaneous group of testicular tumors and paratesticular tumors. In addition, significant changes were also introduced in the 2018 AJCC TNM staging (8th edition) regarding testicular tumors. The germ cell tumors are divided into 2 major groups; tumors derived from germ cell neoplasia in situ (GCNIS) and those unrelated to GCNIS. The GCNIS associated tumors include seminomatous and nonseminomatous germ cell tumors, which constitute a heterogeneous group of tumors. Non-GCNIS-associated tumors include prepubertal-type teratoma, prepubertal yolk sac tumor, mixed prepubertal-type teratoma and yolk sac tumor and spermatocytic seminoma. In the sex cord-stromal category, the tumors are classified based on their cells of origin. Most are Leydig cell tumors and Sertoli cell tumors; however, several mixed and diverse entities based on cell types are included in this group. Gonadoblastoma is the only tumor in the mixed germ cell and sex cord-stromal tumor category. Because of recent advances in molecular techniques, abundant new genetic information has emerged which helped classify the tumors based on the molecular alterations and provided insights into the tumor pathogenesis. This review focused on the updates related to testicular germ cell tumors and sex cord-stromal tumors and described the morphologic, immunohistochemical and molecular characteristics with an aim to provide a practical diagnostic approach and an update on relevant recent molecular advances.


Assuntos
Tumor do Seio Endodérmico/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/patologia , Teratoma/patologia , Neoplasias Testiculares/patologia , Tumor do Seio Endodérmico/genética , Tumor do Seio Endodérmico/metabolismo , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Seminoma/genética , Seminoma/metabolismo , Teratoma/genética , Teratoma/metabolismo , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo
10.
Toxins (Basel) ; 13(3)2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808971

RESUMO

Mammalian animal toxicity of ochratoxin A (OTA) has focused largely in the past half-century on pigs because of initial recognition of it as a principal cause of intermittent growth suppression and renal disease caused by mouldy feed. Subsequent classical toxicology has used laboratory rodents because renal pathology in pigs raised questions concerning possible involvement in the human idiopathic bilateral renal atrophy of Balkan endemic nephropathy for which OTA was a focus of attention for human nephropathy through 1980s and into 2000s. Emphasis on human nephropathy has more recently concerned the plant metabolite aristolochic acid. Recognition that agricultural management can often minimise food and feed-stuff spoilage by OTA-producing Aspergilli and Penicillia has moderated some of the risks for animals. Legislation for human food safety combined with sophisticated analysis generally provides safety in the developed world. Chronic experimental exposure of male rats, in the absence of clinical dis-ease, specifically causes renal cancer. The possibility of this as a unique model for the human has generated considerable experimental evidence which may be more directly relevant for carcinogenesis in the complex kidney than that obtained from biochemical toxicities in vitro. Nevertheless, there does not appear to be any case of human renal or urinary tract cancer for which there is verified etiological proof for causation by OTA, contrary to much claim in the literature. To contribute to such debate, histopathology review of OTA/rat renal cancers, augmented where appropriate by immune profiles, has been completed for all remaining tumours in our research archive. Overall consistency of positivity for vimentin, is matched with occasional positives either for CD10 or the cytokeratin MNF 116. The current situation is discussed. Suggestion that OTA could cause human testicular cancer has also been challenged as unsupported by any experimental findings in rats, where the Leydig cell tumour immune profile does not match that of human germ cell neoplasms.


Assuntos
Testes de Carcinogenicidade , Neoplasias Renais/induzido quimicamente , Ocratoxinas/toxicidade , Neoplasias Testiculares/induzido quimicamente , Animais , Exposição Dietética , Humanos , Queratinas/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Neprilisina/metabolismo , Ratos Endogâmicos F344 , Medição de Risco , Fatores de Risco , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Fatores de Tempo , Vimentina/metabolismo
11.
Biochem Biophys Res Commun ; 557: 55-61, 2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-33862460

RESUMO

Dysregulation of the ubiquitin-proteasome pathway is strongly associated with cancer initiation and progression. Speckle-type POZ(pox virus and zinc finger protein) protein(SPOP) is an adapter protein of CUL3-based E3 ubiquitin ligase complexes. Gene expression profiling from the Cancer Genome Atlas (TCGA) suggests that SPOP is downregulated in testicular germ cell tumors (TGCTs), but the specific contribution of this protein remains to be explored. In this study, we show that the germ line-specific factor DPPA2 was identified as a proteolytic substrate for the SPOP-CUL3-RBX1 E3 ubiquitin-ligase complex. SPOP specifically binds to a SPOP-binding consensus (SBC) degron located in DPPA2 and targets DPPA2 for degradation via the ubiquitin-proteasome pathway. SPOP downregulation increases the expression of pluripotency markers OCT4 and Nanog but decreases that of early differentiation marker gene Fst. This effect is partly dependent on its activity toward DPPA2. In addition, the dysregulation of SPOP-DPPA2 axis contributes to the malignant transformation phenotypes of TGCT cells.


Assuntos
Neoplasias Embrionárias de Células Germinativas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Testiculares/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitinação , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Xenoenxertos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Proteínas Nucleares/genética , Proteólise , Proteínas Repressoras/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia
12.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33800799

RESUMO

Liquid biopsies constitute a minimally invasive means of managing cancer patients, entailing early diagnosis, follow-up and prediction of response to therapy. Their use in the germ cell tumor field is invaluable since diagnostic tissue biopsies (which are invasive) are often not performed, and therefore only a presumptive diagnosis can be made, confirmed upon examination of the surgical specimen. Herein, we provide an overall review of the current liquid biopsy-based biomarkers of this disease, including the classical, routinely used serum tumor markers-the promising microRNAs rapidly approaching the introduction into clinical practice-but also cell-free DNA markers (including DNA methylation) and circulating tumor cells. Finally, and importantly, we also explore novel strategies and challenges for liquid biopsy markers and methodologies, providing a critical view of the future directions for liquid biopsy tests in this field, highlighting gaps and unanswered questions.


Assuntos
Biópsia Líquida , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Procedimentos Clínicos , DNA de Neoplasias/química , Gerenciamento Clínico , Feminino , Humanos , Masculino , MicroRNAs/análise , Proteínas de Neoplasias/análise , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/química , Neoplasias Embrionárias de Células Germinativas/patologia , Células Neoplásicas Circulantes , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/química , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , RNA Neoplásico/análise , Neoplasias Testiculares/sangue , Neoplasias Testiculares/química , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia
13.
Exp Cell Res ; 402(1): 112565, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33744230

RESUMO

Adenylate kinase 6 (AK6), a nucleus localized phosphotransferase in mammalians, shows ubiquitously expression and broad substrate activity in different tissues and cell types. Although the function of AK6 has been extensively studied in different cancer cell lines, its role in mammalian germline is still unknown. Here we showed that knockdown of AK6 inhibits cell proliferation and promotes cell apoptosis in human testicular carcinoma (NT2 cells). Co-immunoprecipitation experiment and in vitro pull down assay identified WNK1 (with no lysine kinase-1) as one of the AK6 interacting proteins in NT2 cells. Moreover, we found that AK6 regulates the phosphorylation states of WNK1 (Thr60) and affects phosphorylation level of Akt (Ser473) upon hypotonic condition, probably affecting chloride channel and regulating ion transport and homeostasis in NT2 cells and consequently contributing to the decreased cell proliferation rate. In conclusion, AK6 regulates WNK1 phosphorylation states and affects ion homeostasis in NT2 cells. These findings provide new insights into the function of AK6 and WNK1 in human testicular carcinoma. This work also provides foundation for further mechanism study of AK6 in spermatogenesis.


Assuntos
Adenilato Quinase/genética , Carcinoma/genética , Proliferação de Células/genética , Neoplasias Testiculares/genética , Apoptose/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Homeostase/genética , Humanos , Masculino , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Neoplasias Testiculares/patologia , Proteína Quinase 1 Deficiente de Lisina WNK/genética
14.
Arch Ital Urol Androl ; 93(1): 64-67, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33754611

RESUMO

INTRODUCTION: Testicular cancers represent about 5% of all urological malignancies and 1-1.5% of all male neoplasms. Most of the testicular cancers are localized (68%) at diagnosis. Bulky masses in the scrotum are rare. We present a rare case of bulky testicular cancer with retroperitoneal spread through the inguinal canal. CASE REPORT: A 44-year-old man came to the emergency department referring weakness and the presence of a scrotal mass. At physical examination, a voluminous mass was found, with necrotic phenomena within the scrotum. Abdomen was tense and sore. Abdominal CT scan revealed a bulky testicular mass spreading to the retroperitoneal space through the inguinal canal with node enlargement. Patient underwent orchiectomy with excision of infiltrated scrotum skin. Histologic diagnosis confirmed a typical form seminoma. The patient was then treated with a cisplatin-based chemotherapy, with a partial response. The patient recently relapsed and he is being treated with a new line of chemotherapy and subsequent surgery with or without radiotherapy. CONCLUSIONS: We described a rare presentation of testicular cancer. This case highlights the importance of a multidisciplinary approach to rare testis tumour presentation and early diagnosis for testicular cancers.


Assuntos
Canal Inguinal/patologia , Neoplasias Retroperitoneais/patologia , Seminoma/patologia , Neoplasias Testiculares/patologia , Adulto , Humanos , Masculino , Invasividade Neoplásica , Neoplasias Retroperitoneais/complicações , Neoplasias Retroperitoneais/terapia , Seminoma/complicações , Seminoma/terapia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/terapia , Úlcera/complicações
15.
J Clin Oncol ; 39(14): 1553-1562, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33729863

RESUMO

PURPOSE: The classification of the International Germ-Cell Cancer Collaborative Group (IGCCCG) has been a major advance in the management of germ-cell tumors, but relies on data of only 660 patients with seminoma treated between 1975 and 1990. We re-evaluated this classification in a database from a large international consortium. MATERIALS AND METHODS: Data on 2,451 men with metastatic seminoma treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Australia, Europe, and North America. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS) calculated from day 1 of treatment. Variables at initial presentation were evaluated for their prognostic impact. Results were validated in an independent validation set of 764 additional patients. RESULTS: Compared with the initial IGCCCG classification, in our modern series, 5-year PFS improved from 82% to 89% (95% CI, 87 to 90) and 5-year OS from 86% to 95% (95% CI, 94 to 96) in good prognosis, and from 67% to 79% (95% CI, 70 to 85) and 72% to 88% (95% CI, 80 to 93) in intermediate prognosis patients. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good prognosis patients with LDH above 2.5× upper limit of normal had a 3-year PFS of 80% (95% CI, 75 to 84) and a 3-year OS of 92% (95% CI, 88 to 95) versus 92% (95% CI, 90 to 94) and 97% (95% CI, 96 to 98) in the group with lower LDH. CONCLUSION: PFS and OS in metastatic seminoma significantly improved in our modern series compared with the original data. The original IGCCCG classification retains its relevance, but can be further refined by adding LDH at a cutoff of 2.5× upper limit of normal as an additional adverse prognostic factor.


Assuntos
Seminoma/mortalidade , Neoplasias Testiculares/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Cooperação Internacional , L-Lactato Desidrogenase/metabolismo , Masculino , Metástase Neoplásica , Prognóstico , Seminoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia
16.
Biomed Environ Sci ; 34(2): 152-162, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33685574

RESUMO

Objective: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed. Methods: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT. Results: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality. Conclusion: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.


Assuntos
Disparidades nos Níveis de Saúde , Neoplasias Embrionárias de Células Germinativas/etnologia , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Testiculares/etnologia , Neoplasias Testiculares/mortalidade , Adulto , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Seminoma/diagnóstico , Seminoma/etnologia , Seminoma/mortalidade , Seminoma/patologia , Taxa de Sobrevida/tendências , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , Estados Unidos/epidemiologia , Estados Unidos/etnologia
19.
Actas urol. esp ; 45(1): 30-38, ene.-feb. 2021. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-200667

RESUMO

INTRODUCCIÓN Y OBJETIVOS: El objetivo de este estudio retrospectivo fue analizar la densidad de los ganglios linfáticos (GL) en la disección de los GL retroperitoneales (DGLRP) para evaluar la masa residual tras quimioterapia como factor predictivo de recurrencia en pacientes con cáncer testicular de células germinales (CTCG). MATERIALES Y MÉTODOS: Se revisaron retrospectivamente los datos de 185 pacientes operados por CTCG entre diciembre del 2004 y febrero del 2017. Se calculó la densidad de los GL. Los pacientes se compararon estadísticamente en términos de características demográficas, características tumorales, niveles de marcadores tumorales séricos, estrategias de tratamiento y resultados patológicos según los subtipos de CTCG. Se realizó un análisis de correlación para determinar los parámetros relacionados con la enfermedad recurrente. RESULTADOS: La mediana de seguimiento fue de 79 (31-179) meses y la mediana de edad de los pacientes fue de 23 (16-71). El tamaño medio del tumor fue de 4 (1-18) cm. Cinco (2,7%) pacientes tenían enfermedad metastásica en el momento del diagnóstico inicial. Se detectó seminoma, TCG no seminomatoso y CTCG de tipo mixto en 62 (33,5%), en 60 (32,4%) y en 63 (34,1%) pacientes, respectivamente. Tras la orquiectomía inguinal, 48 (25,9%) pacientes recibieron seguimiento, 126 (68,1%) pacientes se sometieron a quimioterapia y 11 (5,9%) pacientes recibieron radioterapia. Un total de 21 (11,4%) pacientes se sometieron a DGLRP posquimioterapia. Se observó recurrencia precoz y tardía en 3 (1,6%) y 2 (1,1%) pacientes, respectivamente. Se encontró una correlación negativa leve/moderada, pero significativa, entre la recurrencia y el número de GL con depósitos metastásicos y la densidad de los GL (r = -0,490, p = 0,024 y r = -0,450, p = 0,041, respectivamente). CONCLUSIONES: Hubo una correlación negativa entre el número de GL con depósitos metastásicos y la densidad de GL con la enfermedad recurrente


INTRODUCTION AND OBJECTIVES: In this retrospective study, we aimed to evaluate lymph node (LN) density in retroperitoneal lymph node dissection (RPLND) to analyze whether residual mass after chemotherapy might behave as predicting factor for recurrence in patients with germ cell testicular cancer (GCTC). MATERIALS AND METHODS: The data of 185 patients that were operated between 12/2004 and 02/2017 because of GCTC were reviewed retrospectively. LN density was calculated. The patients were compared statistically in terms of demographic features, tumor characteristics, serum tumor marker levels, treatment strategies, and pathological results according to GCTC subtypes. Correlation analysis was performed to determine the parameters related to recurrent disease. RESULTS: The median follow-up was 79 (31-179) months and the median age of the patients was 23 (16-71). The median tumor size was 4 (1-18) cm. Five (2.7%) patients had metastatic disease at initial diagnosis. Seminoma, non-seminomatous-GCT and mix type-GCTC was detected in 62 (33.5%), 60 (32.4%) and 63 (34.1%) patients, respectively. Following inguinal orchiectomy, 48 (25.9%) patients underwent follow-up, 126 (68.1%) patients underwent chemotherapy and 11 (5.9%) patients underwent radiotherapy. A total of 21 (11.4%) patients underwent post-chemotherapy RPLND. Early and late recurrence was seen in 3 (1.6%) and 2 (1.1%) of the patients, respectively. A mild to moderate, negative, but significant correlation was found between the recurrence and the number of LNs containing metastatic deposits and LN density (r = -0.490, P = .024 and r = -0.450, P=.041, respectively). CONCLUSIONS: There was a negative correlation between the number of LNs containing metastatic deposits and LN density and recurrent disease


Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/patologia , Espaço Retroperitoneal , Centros de Atenção Terciária , Seguimentos , Estadiamento de Neoplasias , Biomarcadores Tumorais , Valores de Referência
20.
Int J Cancer ; 149(1): 158-168, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33634856

RESUMO

Asparaginase (Asp) is one of the most important drugs for treating acute lymphoblastic leukemia (ALL). However, off-protocol Asp administration (OPAA) or hypersensitivity may disturb its pharmacokinetic profile. In this retrospective study, we sought to determine whether OPAA and hypersensitivity to Escherichia coli asparaginase (E coli Asp) impaired extramedullary relapse prevention in a pediatric ALL cohort treated according to SCMC-ALL-2005 protocol from 2005 to 2014 at the Shanghai Children's Medical Center (SCMC). In total, 676 patients were enrolled in this study, including 369 with OPAA and 60 exhibiting hypersensitivity to E coli Asp. At the end of the most recent follow-up, 58 patients had extramedullary relapse. The 5-year cumulative extramedullary relapse incidence in patients with OPAA was 11.01%, whereas that in patients without OPAA was 5.28% (P = .0036). Moreover, the 5-year cumulative extramedullary relapse incidence in patients that exhibited hypersensitivity to E coli Asp was 16.48%, whereas that in patients without hypersensitivity was 7.59% (P = .0195). Concerning the relapse site, OPAA not only increased central nervous system (CNS) relapse but testicular relapse as well. Based on Fine and Gray multivariate analysis, OPAA and hypersensitivity to Asp were independent risk factors for extramedullary relapse. In conclusion, to prevent extramedullary relapse of ALL, adequate duration to administrate Asp was more important than the total dosage, and more attention should be paid to Asp inadequate due to hypersensitivity.


Assuntos
Asparaginase/administração & dosagem , Linfócitos B/efeitos dos fármacos , Neoplasias do Sistema Nervoso Central/prevenção & controle , Recidiva Local de Neoplasia/prevenção & controle , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Neoplasias Testiculares/prevenção & controle , Adolescente , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , China , Escherichia coli/enzimologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Testiculares/patologia
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