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1.
Stem Cell Res Ther ; 15(1): 128, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693576

RESUMO

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.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs , Proteína Homeobox Nanog , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Proteína Homeobox Nanog/metabolismo , Proteína Homeobox Nanog/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/genética , Masculino , Linhagem Celular Tumoral , Proliferação de Células/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Cisplatino/farmacologia
3.
Oncology (Williston Park) ; 38(4): 142-146, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38661513

RESUMO

A 41-year-old man presented to his primary care physician with a 1-month history of left neck adenopathy in the context of a history of nonseminomatous germ cell tumors (NSGCTs). In 2011, the patient was treated for stage IB (T2N0M0S0) right-sided NSGCTs of the testis, which were 95% embryonal and 5% yolk sac tumors. He underwent a right radical orchiectomy and was followed until 2022 without recurrence. In the work-up for his adenopathy, laboratory results for human chorionic gonadotropin, lactate dehydrogenase, and α-fetoprotein were normal. CT scans confirmed clustered enlarged lymph nodes in the left lower spinal accessory posterior triangle, enlarged left lower neck lymph nodes, and several foci of enlarged left retroperitoneal periaortic lymph nodes. Fine needle aspiration of a left neck lymph node identified malignant tumor cells. A left neck dissection showed embryonal carcinoma in 12 of 28 nodes. Immunostaining showed the tumor cells were positive for SALL4 and CD30 but negative for CD117. This patient likely had a contralateral late relapse of his original right NSGCT after 11 years of remission. The patient's original cancer was on the right side, with recurrence surrounding the aorta on the contralateral side, representing an atypical pattern of spread.


Assuntos
Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/patologia , Neoplasias Testiculares/terapia , Neoplasias Testiculares/cirurgia , Adulto , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Recidiva Local de Neoplasia/patologia , Orquiectomia , Metástase Linfática
4.
Anticancer Res ; 44(5): 2151-2157, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677742

RESUMO

BACKGROUND/AIM: While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) benefits patients with teratoma or viable germ cell tumors (GCT), it becomes overtreatment if necrosis is detected in PC-RPLND specimens. Serum microRNA-371a-3p correctly predicts residual viable GCT with 100% sensitivity; however, prediction of residual teratoma in PC-RPLND specimens using current modalities remains difficult. Therefore, we developed a machine learning model using CT imaging and clinical variables to predict the presence of residual teratoma in PC-RPLND specimens. PATIENTS AND METHODS: This study included 58 patients who underwent PC-RPLND between 2005 and 2019 at the University of Tsukuba Hospital. On CT imaging, 155 lymph nodes were identified as regions of interest (ROIs). The ResNet50 algorithm and/or Support Vector Machine (SVM) classification were applied and a nested, 3-fold cross-validation protocol was used to determine classifier accuracy. RESULTS: PC-RPLND specimen analysis revealed 35 patients with necrosis and 23 patients with residual teratoma, while histology of 155 total ROIs showed necrosis in 84 ROIs and teratoma in 71 ROIs. The ResNet50 algorithm, using CT imaging, achieved a diagnostic accuracy of 80.0%, corresponding to a sensitivity of 67.3%, a specificity of 90.5%, and an AUC of 0.84, whereas SVM classification using clinical variables achieved a diagnostic accuracy of 74.8%, corresponding to a sensitivity of 59.0%, a specificity of 88.1%, and an AUC of 0.84. CONCLUSION: Our machine learning models reliably distinguish between necrosis and residual teratoma in clinical PC-RPLND specimens.


Assuntos
Excisão de Linfonodo , Aprendizado de Máquina , Teratoma , Humanos , Masculino , Adulto , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/diagnóstico por imagem , Espaço Retroperitoneal/cirurgia , Teratoma/patologia , Teratoma/cirurgia , Teratoma/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/diagnóstico por imagem , Adulto Jovem , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem
5.
Ann Ital Chir ; 95(2): 119-125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38684493

RESUMO

INTRODUCTION: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignant tumor, with nonspecific clinical symptoms and radiological features. Less than 150 cases have been reported in adults across the world. PRESENTATION OF CASE: We report a case of an extremely rare subtype of UESL with epithelioid features in a 29-year-old woman, presenting as a cystic lesion of 27 × 17 cm, completely subverting the right hepatic lobe. She underwent a right hepatectomy with anterior approach, complete hilum lymphadenectomy and partial diaphragmatic resection for local infiltration, followed by systemic chemotherapy. She remains with no evidence of disease and liver mass has been restored after 6 months. DISCUSSION: The present case report represents the second case of UESL with epithelioid features described across the world. The immunohistochemical expression pattern, cytokeratin (CK)19 + and CK7 -, strongly suggests an origin of this epithelioid component from native biliary cells and not from a reshaped ductal plate. Due to the rarity of this form, to date it is impossible to define the prognostic impact of this subtype of UESL, and treatment remains challenging. CONCLUSION: UESL is associated with a poor prognosis, especially in adults, but a comprehensive and multidisciplinary treatment based on radical resection and adjuvant therapy may provide a survival benefit. Surgical excision with negative margins remains mandatory to diagnose and treat UESL.


Assuntos
Hepatectomia , Neoplasias Hepáticas , Doenças Raras , Sarcoma , Humanos , Adulto , Feminino , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Sarcoma/patologia , Sarcoma/cirurgia , Sarcoma/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Células Epitelioides/patologia
6.
J Intern Med ; 295(6): 715-734, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38468475

RESUMO

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs. The 5-year overall survival in ovarian GCTs was 85.2%, versus 98.2% for testicular GCTs. How can this be explained? One reason may be the difference in knowledge, experience, and evidence because the incidence rate of testicular cancer is more than 15 times that of ovarian GCTs. Given the rarity of the disease in women and the lack of established guidelines, a comprehensive understanding of the disease and treatment decisions is challenging. The main objective of this review is to derive insights from testicular GCTs (seminoma and non-seminoma) by reviewing etiological, tumor biological, and clinical knowledge, and to thereafter suggest actions for ovarian GCTs based on this. We hypothesize that by adopting specific treatment strategies from testicular GCTs-including de-escalating adjuvant chemotherapy for low-risk patients and implementing more standardized and intensive treatment protocols in cases of relapse-we can improve the prognosis and minimize long-term side effects in ovarian GCT patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Neoplasias Testiculares , Humanos , Neoplasias Testiculares/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia , Masculino , Prognóstico , Feminino
7.
Clin Oncol (R Coll Radiol) ; 36(6): 370-377, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38555208

RESUMO

AIMS: To evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). METHODS: A retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. RESULTS: Yolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I-II and stages III-IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1-2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). CONCLUSION: Distinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/terapia , Adulto , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Prognóstico , Estudos de Coortes , Taxa de Sobrevida
8.
Zhonghua Fu Chan Ke Za Zhi ; 59(3): 210-214, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38544450

RESUMO

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 µg/L) were significantly higher than normal (<25 µg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.


Assuntos
Tumor do Seio Endodérmico , Neoplasias Embrionárias de Células Germinativas , Neoplasias Ovarianas , Gravidez , Criança , Humanos , Feminino , Adulto Jovem , Adulto , Adolescente , alfa-Fetoproteínas/uso terapêutico , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/cirurgia , Estudos Retrospectivos , Estadiamento de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/etiologia , Neoplasias Embrionárias de Células Germinativas/patologia
9.
Curr Oncol Rep ; 26(4): 318-335, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38430323

RESUMO

PURPOSE OF REVIEW: This narrative review provides a comprehensive overview of the evolving role of retroperitoneal lymph node dissection (RPLND) in the management of testicular cancer (TC). It explores the significance of RPLND as both a diagnostic and therapeutic tool, highlighting its contribution to accurate staging, its impact on oncological outcomes, and its influence on subsequent treatment decisions. RECENT FINDINGS: RPLND serves as an essential diagnostic procedure, aiding in the precise assessment of lymph node involvement and guiding personalized treatment strategies. It has demonstrated therapeutic value, particularly in patients with specific risk factors and disease stages, contributing to improved oncological outcomes and survival rates. Recent studies have emphasized the importance of meticulous patient selection and nerve-sparing techniques to mitigate complications while optimizing outcomes. Additionally, modern imaging and surgical approaches have expanded the potential applications of RPLND. In the context of TC management, RPLND remains a valuable and evolving tool. Its dual role in staging and therapy underscores its relevance in contemporary urological practice. This review highlights the critical role of RPLND in enhancing patient care and shaping treatment strategies, emphasizing the need for further research to refine patient selection and surgical techniques.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/tratamento farmacológico , Espaço Retroperitoneal/patologia , Espaço Retroperitoneal/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Linfonodos/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Estadiamento de Neoplasias
10.
Appl Neuropsychol Child ; 13(2): 180-189, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447131

RESUMO

Survivors of pediatric brain tumors are at high risk for long-term neuropsychological difficulties. In the current case study, we present longitudinal neuropsychological data spanning 10 years (from age 9 to 19 years) of a patient with a rare, very large, bifrontal, embryonal tumor with abundant neuropil and true rosettes (ETANTR), which is typically associated with poor survivorship and significant neurological impact. Results demonstrated that the patient had largely intact cognitive functioning with specific difficulties in executive functioning, fine motor skills, and adaptive functioning at her most recent neuropsychology 10-year follow-up. These results highlight outcomes for a patient with remarkable resiliency in the context of numerous risk factors (a very large tumor size, multi-modal treatment, and seizure history). Patient protective factors (a high level of cognitive reserve, family support, and appropriate comprehensive educational services) likely contributed to the patient's favorable neuropsychological outcome. The patient's age at brain tumor diagnosis (9 years) and associated treatment was at a critical period of development for emerging higher order cognitive functions which likely impacted acquisition of executive functioning skills and secondarily adaptive skill outcomes. Consequently, pediatric brain tumor survivors with ETANTR or other frontal tumors require targeted screening of executive functions and proactive interventions.


Assuntos
Neoplasias Encefálicas , Neoplasias Embrionárias de Células Germinativas , Criança , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Neoplasias Encefálicas/complicações , Neurópilo/patologia , Função Executiva , Neoplasias Embrionárias de Células Germinativas/patologia , Cognição , Testes Neuropsicológicos
12.
Urol Oncol ; 42(4): 102-109, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38360519

RESUMO

To evaluate the oncological outcomes and safety of primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) II seminomatous testicular germ cell tumor (TGCT). A literature search using PubMed, Scopus, and Cochrane Library was conducted on July 2023 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. The pooled recurrence rate and treatment-related complications were calculated using a random effects model. Overall 8 studies published between 1997 and 2023 including a total of 355 patients were selected for systematic review and meta-analysis with the overall median follow-up of 38 months. The overall and infield recurrence rate were 0.14 (95% CI: 0.08-0.22) and 0.04 (95% CI: 0.00-0.11), respectively. The overall pooled rate of ≥ Clavien Dindo grade III complications was 0.04 (95% CI: 0.01-0.10); there was no significant heterogeneity (I^2 = 35.10%, P = 0.19). Antegrade ejaculation was preserved with the overall pooled rate of 0.98 (95% CI: 0.95-1.00); there was no significant heterogeneity on Chi-square and I2 tests (I^2 = 0.00%, P = 0.58). Primary RPLND is a safe and effective treatment option for patients with CS II seminomatous TGCT resulting highly promising cure rates combined with low treatment-associated adverse events, at medium-term follow-up. However, owing to the lack of comparative studies to the current standard of care and the limited follow-up, individual decision must be made with the informed patient in a shared decision process together with a multidisciplinary team.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/patologia , Espaço Retroperitoneal/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/patologia , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Neoplasias Testiculares/patologia , Resultado do Tratamento , Estudos Retrospectivos , Estadiamento de Neoplasias
13.
Histopathology ; 84(7): 1199-1211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38409885

RESUMO

AIMS: Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown. METHODS AND RESULTS: In this study, 47 patients were enrolled and their tumour specimens were analysed by whole-exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression-free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance. CONCLUSION: This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.


Assuntos
Neoplasias Encefálicas , Sequenciamento do Exoma , Neoplasias Embrionárias de Células Germinativas , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Feminino , Adolescente , Criança , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Pré-Escolar , China/epidemiologia , Adulto , Adulto Jovem , Variações do Número de Cópias de DNA , Mutação , Povo Asiático/genética , Proteína Reelina , Biomarcadores Tumorais/genética , Prognóstico , População do Leste Asiático
14.
Ann Surg Oncol ; 31(5): 3544-3553, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38381210

RESUMO

BACKGROUND: Existing data on the histopathological correlation of testicular tumors with lymph node prognosis have been poorly explored. We aimed to investigate the relationship of the histopathological properties of testicular tumors with lymph nodes and their involvement with chemoresistance and heterogeneity of testicular tumors. METHODS: Patients with non-seminomatous germ cell tumor (NSGCT) were selected for histopathological correlation of testicular tumor with lymph nodes and its relationship with chemoresistance and heterogeneity. Histopathological and radiological parameters associated with the risk of chemoresistance and tumor progression were measured pre- and post-chemotherapy. Binomial logistic regression and Kaplan-Meier analysis were implemented to determine the predictors of progression and adverse overall patient survival. All categorical variables were analyzed using the Chi-square test, while Pearson's R coefficient determined the correlation. RESULTS: Male patients who were diagnosed with NSGCT from March 2017 to December 2018 at Guwahati Medical College, Guwahati, India, were included in this study. Lymph node groups were predominantly incriminated with the EYST or EYS groups and minimally linked with the pure E and YCS groups. Furthermore, the highest number of lymph node stations was associated with pre-chemotherapy. In salvage chemotherapy in the form of VIP, we found exciting outcomes, as approximately 41% of cases responded positively, especially in the EYS group. CONCLUSION: Our study classifies NSGCT according to the most favorable histopathological grouping and explores the tumoral response in different intrinsic and extrinsic variables. Our analysis can serve as a triumphant histopathological nomogram for a sublime management protocol to deal with the onerous histological pairing in NSGCT.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Resistencia a Medicamentos Antineoplásicos , Estudos Retrospectivos , Linfonodos/patologia , Prognóstico , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Excisão de Linfonodo , Espaço Retroperitoneal/patologia , Proteínas do Olho/uso terapêutico
15.
Curr Opin Urol ; 34(3): 204-209, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305430

RESUMO

PURPOSE OF REVIEW: Recent advancements in the management of clinical stage II (CS II) testicular cancer have transformed it into a predominantly curable condition. This success in treatment advancements has markedly extended patient survival. However, these treatments carry risks and morbidities, which is important to consider given the disease's impact on young men and the emerging understanding of long-term treatment consequences. RECENT FINDINGS: Emerging data support primary retroperitoneal lymph node dissection (RPLND) for select CS II seminoma patients, with similar short-term outcomes to chemotherapy but less treatment intensity. Recent studies have also challenged the reflexive use of adjuvant chemotherapy for pathologic node-positive disease, as growing evidence shows low relapse rates regardless of nodal stage. Furthermore, novel biomarkers like circulating serum microRNA-371a-3p levels can help predict the presence of viable germ cell tumor at time of RPLND. SUMMARY: Advances in risk stratification and therapy enable personalized de-escalation approaches for oligometastatic testicular cancer, optimizing survivorship. Upfront RPLND, reassessing adjuvant systemic therapy for RPLND pN+ disease, and novel biomarkers will shape precision treatment to achieve high cure rates with excellent quality of life. Ongoing trials of reduced-intensity regimens, accurate prognostic models, improved surgical strategy, and emerging biomarkers represent the next frontier in tailored curative therapy.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/patologia , Qualidade de Vida , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Excisão de Linfonodo/efeitos adversos , Resultado do Tratamento , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/patologia , Biomarcadores , Espaço Retroperitoneal/cirurgia , Estudos Retrospectivos
16.
Jpn J Clin Oncol ; 54(5): 592-598, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38369557

RESUMO

BACKGROUND: In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM). RESULTS: Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P < 0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P < 0.001) were independent predictors of higher OM, relative to good prognosis group. CONCLUSIONS: The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large.


Assuntos
Programa de SEER , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Adulto , Prognóstico , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Taxa de Sobrevida , Adulto Jovem , Metástase Neoplásica
17.
Int Urol Nephrol ; 56(6): 1887-1898, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38285100

RESUMO

PURPOSE: Testicular Germ Cell Tumors (TGCTs) are the most frequent solid malignancies in young adult men. Regardless of differences in their cell of origin, all TGCTs are considered highly curable malignancies. However, approximately 3-5% of all TGCTs do not respond to platinum-based chemotherapies. The purpose of our paper is to investigate whether immunohistochemical expression of MLH1 and REV-7 can be used as predictive tissue markers for TGCTs. MATERIAL AND METHODS: The main demographic and clinicopathological characteristics of 64 male patients with TGCTs who underwent orchiectomy from 2007 to 2022 were retrospectively obtained from two large Oncology Clinics in Greece. Both patients with chemosensitive and chemoresistant disease were included. Immunohistochemical staining for MLH1 and REV-7 proteins was applied in specimens of these patients. RESULTS: 31 seminomas and 33 non-seminomas were included. 48 patients had chemosensitive disease, while 16 had chemoresistant disease. 53 specimens showed preserved MLH1 expression, while 11 specimens had lost MLH1 expression. Expression of MLH1 was only significantly associated with patients' age. 16 specimens showed positive REV-7 expression, while 48 specimens were REV-7 negative. Interestingly, 50% of patients with chemoresistant disease and 16,7% of patients with chemosensitive disease were REV-7 positive. This difference was statistically significant. Moreover, REV-7 positivity was significantly associated with chemoresistance, various clinicopathological parameters and patients' prognosis and survival. CONCLUSION: Loss of MLH1 expression was only found to be significantly associated with lower patients' age. Positive immunohistochemical REV-7 expression was significantly associated with various clinicopathological parameters, while it was also associated with significantly lower survival and greater hazard. REV-7 positive percentages were significantly higher in patients with chemoresistant disease. Our findings imply that immunohistochemical staining for REV-7 could potentially be used as a predictive tissue marker for TGCT tumors. Moreover, targeting of REV-7 protein, could represent a potential therapeutic strategy for chemoresistant TGCT cases. The implementation of well-designed studies on a larger scale is of utmost importance, in order to draw safer conclusions. Additional studies are needed so as to draw safer conclusions.


Assuntos
Biomarcadores Tumorais , Imuno-Histoquímica , Proteína 1 Homóloga a MutL , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Proteína 1 Homóloga a MutL/metabolismo , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/patologia , Adulto , Estudos Retrospectivos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Pessoa de Meia-Idade , Adulto Jovem , Valor Preditivo dos Testes , Prognóstico , Seminoma/metabolismo , Seminoma/patologia
18.
BJU Int ; 133(6): 717-724, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38293778

RESUMO

OBJECTIVES: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. PATIENTS AND METHODS: Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. RESULTS: Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. CONCLUSIONS: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.


Assuntos
Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Testiculares/patologia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/terapia , Estudos Prospectivos , Adulto , Adulto Jovem , Tomografia Computadorizada por Raios X , Excisão de Linfonodo , Biomarcadores Tumorais , Pessoa de Meia-Idade , Adolescente , Metástase Linfática , Suécia/epidemiologia
19.
J Surg Res ; 295: 423-430, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38070256

RESUMO

INTRODUCTION: Surveillance following sacrococcygeal teratoma (SCT) resection varies. The purpose of this study was to describe the clinical characteristics and outcomes of patients undergoing SCT resection and examine current institutional practices to detect recurrence. METHODS: A single-institution retrospective review of children who underwent resection of an SCT from January 1, 2010 to December 31, 2020 was performed. Data were summarized and surveillance strategies compared between histopathologic subtypes using nonparametric methods. RESULTS: Thirty six patients (75.0% female) underwent SCT removal at a median age of 8 d. Histopathology revealed 27 mature teratomas (75.0%), eight immature teratomas (22.2%), and one malignant germ cell tumor (2.8%). Median postoperative follow-up was 3.17 y (interquartile range [IQR]: 2.31-4.38 y). Patients had a median of 2.32 clinic visits per year (IQR: 2.00-2.70), alpha-fetoprotein levels were obtained at a median of 2.01 times per year (IQR: 0-1.66), and surveillance imaging was performed at a median of 2.31 times per year (IQR: 0-2.84). Patients with immature teratomas had alpha-fetoprotein laboratories obtained more frequently than patients with mature teratomas (3.10 times/year versus 0.93 times/year, P = 0.001). There was no significant difference in the number of imaging studies obtained between groups. Two patients (5.6%) developed recurrence, which were identified on magnetic resonance imaging at 191 and 104 d postresection, respectively. CONCLUSIONS: Postoperative surveillance practices varied widely. Recurrence was noted in a single malignant case in the first year following resection. Multi-institutional studies are needed to determine the optimal surveillance strategy to detect recurrence of SCT.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Pélvicas , Teratoma , Criança , Humanos , Feminino , Masculino , alfa-Fetoproteínas , Região Sacrococcígea/patologia , Região Sacrococcígea/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Pélvicas/patologia
20.
Asian J Endosc Surg ; 17(1): e13262, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37944943

RESUMO

For patients with testicular tumors who need the surgical management, open retroperitoneal lymph node dissection (O-RPLND) is considered the gold standard treatment. However, recently, robot-assisted RPLND (R-RPLND) has gained popularity as a minimally invasive therapy alternative to O-RPLND and laparoscopic RPLND. Here, we report the case of a 32-year-old man presenting with a left testicular teratoma with several enlarged left para-aortic lymph nodes. After the orchiectomy, the patient underwent R-RPLND with an operation time of 279 min, console time of 189 min, bleeding volume of 59 mL, and no significant complications, resulting in a successful outcome. To the best of our knowledge, this is the first reported case of R-RPLND in Japan. Based on our experience, R-RPLND may provide safe and effective outcomes; however, further research is required before the widespread implementation of this technique.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Robótica , Neoplasias Testiculares , Masculino , Humanos , Adulto , Japão , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/patologia , Estadiamento de Neoplasias , Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Espaço Retroperitoneal/cirurgia , Resultado do Tratamento , Estudos Retrospectivos
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