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1.
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
2.
Medicine (Baltimore) ; 103(8): e37213, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38394499

RESUMO

Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias Embrionárias de Células Germinativas , Humanos , Masculino , Adulto , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Paclitaxel/uso terapêutico , Transplante Autólogo , Etoposídeo , Terapia de Salvação
3.
Hawaii J Health Soc Welf ; 83(2): 45-47, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344694

RESUMO

Thyrotoxicosis as the presenting syndrome of an underlying ß-hCG-secreting malignancy is well described. It has been previously theorized, but not reported, that the surge of ß-hCG secondary to chemotherapy induction may inadvertently trigger thyrotoxicosis. After thorough review, this is the first documented case of such event in peer-reviewed medical literature published in the English language. This is a case of a 21-year-old male with stage IIIc non-seminomatous germ cell tumor who developed paraneoplastic hyperthyroidism within 4 days of the first cycle of chemotherapy. Management considerations are suggested based on this case and review of the literature.


Assuntos
Antineoplásicos , Hipertireoidismo , Neoplasias Embrionárias de Células Germinativas , Tireotoxicose , Masculino , Humanos , Adulto Jovem , Adulto , Gonadotropina Coriônica/metabolismo , Gonadotropina Coriônica/uso terapêutico , Hipertireoidismo/induzido quimicamente , Hipertireoidismo/complicações , Tireotoxicose/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Antineoplásicos/uso terapêutico
4.
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
7.
Clin Genitourin Cancer ; 22(1): 33-37, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37468341

RESUMO

INTRODUCTION: Testicular germ cell tumors are the most common malignancy in young adult males. Patients with metastatic disease receive standard of care chemotherapy followed by retroperitoneal lymph node dissection for residual masses >1cm. However, there is a need for better preoperative tools to discern which patients will have persistent disease after chemotherapy given low rates of metastatic germ cell tumor after chemotherapy. The purpose of this study was to use radiomics to predict which patients would have viable germ cell tumor or teratoma after chemotherapy at time of retroperitoneal lymph node dissection. PATIENTS AND METHODS: Patients with nonseminomatous germ cell tumor undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) between 2008 and 2019 were queried from our institutional database. Patients were included if prechemotherapy computed tomography (CT) scan and postchemotherapy imaging were available. Semiqualitative and quantitative features of residual masses and nodal regions of interest and radiomic feature extractions were performed by 2 board certified radiologists. Radiomic feature analysis was used to extract first order, shape, and second order statistics from each region of interest. Post-RPLND pathology was compared to the radiomic analysis using multiple t-tests. RESULTS: 45 patients underwent PC-RPLND at our institution, with the majority (28 patients) having stage III disease. 24 (53%) patients had teratoma on RPLND pathology, while 2 (4%) had viable germ cell tumor. After chemotherapy, 78%, 53%, and 33% of patients had cystic regions, fat stranding, and local infiltration present on imaging. After radiomic analysis, first order statistics mean, median, 90th percentile, and root mean squares were significant. Strong correlations were observed between these 4 features;a lower signal was associated with positive pathology at RPND. CONCLUSIONS: Testicular radiomics is an emerging tool that may help predict persistent disease after chemotherapy.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Masculino , Adulto Jovem , Humanos , Resultado do Tratamento , Espaço Retroperitoneal/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Excisão de Linfonodo/métodos , Teratoma/diagnóstico por imagem , Teratoma/tratamento farmacológico , Teratoma/cirurgia
8.
J Urol ; 211(3): 426-435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38085711

RESUMO

PURPOSE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival. MATERIALS AND METHODS: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification. RESULTS: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups (P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001). CONCLUSIONS: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Humanos , Masculino , Espaço Retroperitoneal/patologia , Recidiva Local de Neoplasia/cirurgia , Excisão de Linfonodo/métodos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Teratoma/tratamento farmacológico , Teratoma/cirurgia , Teratoma/patologia , Necrose , Estudos Retrospectivos
9.
BMJ Open ; 13(12): e074963, 2023 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072472

RESUMO

INTRODUCTION: Bleomycin is a crucial and irreplaceable chemotherapy regimen for malignant ovarian germ cell tumours (MOGCTs) but its toxicities especially pulmonary fibrosis have limited the dose of treatment efficacy and decreased the patients' quality of life (QoL). Nintedanib has been approved for treating progressive fibrosing interstitial lung diseases and has shown potential anti-tumour effects. This study aims to evaluate the effectiveness and safety of nintedanib in the prevention of pulmonary fibrosis induced by bleomycin in MOGCTs patients. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. We will enrol a total of 128 patients who will be randomly assigned to the nintedanib group and placebo group in a 1:1 ratio. Standard bleomycin, etoposide and cisplatin chemotherapy will be given to each MOGCT patient. In addition, patients assigned to nintedanib and the control group will be given oral nintedanib 150 mg two times per day and placebo one tablet two times per day until 1 month after the last cycle of bleomycin therapy, respectively. The primary outcome is the decline of forced vital capacity (FVC). The secondary outcomes are the decline of other pulmonary function indices (forced expiratory volume in 1 s; FVC pred%, carbon monoxide diffusion capacity) and the patients' QoL, oncological and fertility outcomes. We will use electronic case report forms to record all the participants' data and SPSS V.27.0/STATA V.16.0/Graphpad Prism V.8.0 to conduct statistical analysis. ETHICS AND DISSEMINATION: The Ethics Committee of Peking Union Medical College Hospital has approved the study (I-23PJ400). Written informed consent will be obtained from all participants/guardians. Study results will be submitted to peer-reviewed medical journals for publication and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300070492.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Fibrose Pulmonar , Feminino , Humanos , Qualidade de Vida , Bleomicina/efeitos adversos , Método Duplo-Cego , Resultado do Tratamento , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
10.
Hinyokika Kiyo ; 69(9): 259-264, 2023 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-37794677

RESUMO

A 23-year-old male was aware of pain around his left hip joint and visited a nearby orthopedic clinic. Swelling of the right testis was pointed out, and a testicular tumor was suspected. He was referred to the urology department of a local hospital. Blood analysis showed an increase of α-fetoprotein (AFP) (3,620 ng/ml). Computed tomographic (CT) -scan revealed a left iliac bone metastasis and morbid fracture. Right radical inguinal orchiectomy was performed. The pathological examination revealed mixed germ cell tumor (embryonic carcinoma and immature teratoma: 70%, seminoma: 30%). The diagnosis was non-seminomatous germ cell tumor, stage IIIc, and poor risk on the International Germ Cell Consensus Classification. After one cycle of a bleomycin, etoposide and cisplatinum (BEP) regimen, he was referred to our hospital. After a total of 4 cycles of BEP, AFP was normalized. Denosumab was also administered monthly. The CT-scan showed a reduction of bone metastasis and recovery of ossification. Bone biopsy did not show viable tumor cells. Because extirpation of the remaining mass would require resection of the left part of the pelvic bone with significant functional loss of the left limb, we performed close follow-up after an additional 2 courses of the etoposide and cisplatin regimen. The patient is currently alive without recurrence at 45 months after the last systemic chemotherapy.


Assuntos
Neoplasias Ósseas , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Adulto Jovem , Adulto , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Etoposídeo/uso terapêutico , alfa-Fetoproteínas/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Bleomicina/uso terapêutico , Orquiectomia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico
11.
Pediatr Blood Cancer ; 70(12): e30697, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37798818

RESUMO

PURPOSE: Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment. METHODS: We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum. RESULTS: Fourteen patients were included (median age = 12 months), of which six (43%) were classified as HiR. AFP levels were normalized after first-line chemotherapy in all cases but one. A vaginal post-chemotherapy residuum (median size = 8 mm, range: 1-24 mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow-up (median = 4.6 years, range: 0.5-16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy). CONCLUSION: Childhood vaginal MGCTs show a highly favorable prognosis with risk-adapted chemotherapy and local treatment of post-chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Vaginais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , alfa-Fetoproteínas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina , Cisplatino , Progressão da Doença , Etoposídeo , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Resultado do Tratamento , Neoplasias Vaginais/tratamento farmacológico
12.
J Clin Oncol ; 41(34): 5296-5305, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656935

RESUMO

PURPOSE: No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes. METHODS: Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions. All patients had viable nonteratomatous germ cell tumor in the pcRPLND specimen. Surgery was performed after a median of 57 days, followed by either surveillance (n = 64) or adjuvant chemotherapy (n = 53). Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: After controlling for International Germ Cell Cancer Cooperative Group risk group and percent of viable malignant cells found at RPLND, no difference was observed between men managed with surveillance or adjuvant chemotherapy regarding PFS (hazard ratio [HR], 0.72 [95% CI, 0.32 to 1.6]; P = .4), CSS (HR, 0.69; 95% CI, 0.20 to 2.39; P = .6), and OS (HR, 0.78 [95% CI, 0.25 to 2.44]; P = .7). No statistically significant differences for PFS, CSS, or OS were observed on the basis of chemotherapy regimen or in men treated with pcRPLND ≤57 versus >57 days after first-line chemotherapy. Residual disease with <10% versus ≥10% viable cancer cells were associated with a longer PFS (HR, 3.22 [95% CI, 1.29 to 8]; P = .012). Relapse in the retroperitoneum was observed in 34 (29%) men. CONCLUSION: Men with a complete resection at pcRPLND and <10% viable cells have favorable outcomes without further treatment. Complete retroperitoneal resection seems more important than early pcRPLND.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Feminino , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Neoplasia Residual , Estudos Retrospectivos , Excisão de Linfonodo , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Espaço Retroperitoneal/patologia , Fatores de Risco , Recidiva , Resultado do Tratamento
13.
Medicine (Baltimore) ; 102(37): e35120, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713839

RESUMO

In recent years, there has been growing evidence linking mitochondrial dysfunction to the development and progression of cancer. However, the role of mitochondrial metabolism-related genes (MMRGs) in testicular germ cell tumor (TGCT) remains unclear. We downloaded clinical pathology, transcriptome, and somatic mutation data for TGCT from public databases and conducted univariate Cox regression analysis to investigate prognostic correlations. We also used consensus clustering to identify molecular subtypes, comparing differential expression genes, biological processes, Kyoto Encyclopedia of Genes and Genomes pathways, mutations, prognosis, immune infiltration, drug sensitivity, and immune therapeutic response between these subtypes. We constructed multi-gene risk features and nomograms for TGCT prognosis. Fifteen MMRGs were significantly correlated with progression-free survival in TGCT patients. Based on these genes, we identified 2 molecular subtypes which showed significant differences in somatic mutations, prognosis, and immune cell infiltration. These subtypes could also indicate drug sensitivity and immune therapeutic response; the subtype with poor prognosis showed a higher potential benefit from some drugs and immunotherapy. Abnormalities in immune-related biological processes and extracellular matrix as well as Kyoto Encyclopedia of Genes and Genomes pathways such as PI3K-AKT signaling pathway, pat5hways in cancer, primary immunodeficiency, and neutrophil extracellular trap formation were associated with significant differences in phenotypes among subtypes. Finally, we constructed an 8-gene TGCT risk feature based on differential expression genes between subtypes which performed well in TGCT patient prognostic evaluation. Our study elucidated the prognostic correlation between MMRGs and TGCT and established MMRG-derived molecular subtypes and risk features for personalized treatment of TGCT which have potential clinical application value.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Masculino , Fosfatidilinositol 3-Quinases , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/genética , Mitocôndrias/genética , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/genética
14.
Cancer ; 129(24): 3952-3961, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37715631

RESUMO

BACKGROUND: High-dose carboplatin is an essential part of curative high-dose chemotherapy (HDCT) for patients with previously treated germ cell tumors (GCTs). Although hearing loss (HL) is a known side effect of HDCT, data on its severity and characteristics are limited. METHODS: Eligible patients received HDCT for GCTs from 1993 to 2017 and had audiograms before and after HDCT. HL severity was classified by American Speech-Language-Hearing Association criteria, and mean change in hearing threshold at each frequency (0.25-8 kHz) was estimated from pre- to post-HDCT and between HDCT cycles. RESULTS: Of 115 patients (median age, 32 years), 102 (89%) received three cycles of HDCT. Of 106 patients with normal hearing to mild HL in the speech frequencies (0.5-4 kHz) before HDCT, 70 (66%) developed moderate to profound HL in the speech frequencies after HDCT. Twenty-five patients (22%) were recommended for hearing aids after HDCT. Patients with moderate to profound HL isolated to the higher frequencies (6-8 kHz) before HDCT were more likely to develop moderate to profound HL in the speech frequencies after HDCT (94% vs. 61%; p = .01) and to be recommended for hearing aids (39% vs. 18%; p = .05). CONCLUSIONS: HL was frequent after HDCT for GCTs, with most patients developing at least moderate HL in the speech frequencies and approximately one in five recommended for hearing aids. Moderate to profound HL isolated to high frequencies at baseline was predictive of more clinically significant hearing impairment after HDCT. PLAIN LANGUAGE SUMMARY: Some patients with germ cell tumors, the most common malignancy in adolescent and young adult men, are not cured with standard-dose chemotherapy and require high-dose chemotherapy (HDCT). Using detailed hearing assessments of patients receiving HDCT, we found that most patients developed significant hearing loss and that one in five needed hearing aids. Thus, strategies to reduce this side effect are urgently needed, and all patients receiving HDCT should have a hearing test after therapy.


Assuntos
Perda Auditiva , Neoplasias Embrionárias de Células Germinativas , Ototoxicidade , Masculino , Adolescente , Adulto Jovem , Humanos , Adulto , Carboplatina/efeitos adversos , Ototoxicidade/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/etiologia , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia
16.
Br J Cancer ; 129(10): 1580-1589, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37726478

RESUMO

BACKGROUND: Germ cell tumors (GCT) might undergo transformation into a somatic-type malignancy (STM), resulting in a cell fate switch to tumors usually found in somatic tissues, such as rhabdomyosarcomas or adenocarcinomas. STM is associated with a poor prognosis, but the molecular and epigenetic mechanisms triggering STM are still enigmatic, the tissue-of-origin is under debate and biomarkers are lacking. METHODS: To address these questions, we characterized a unique cohort of STM tissues on mutational, epigenetic and protein level using modern and high-throughput methods like TSO assays, 850k DNA methylation arrays and mass spectrometry. RESULTS AND CONCLUSIONS: For the first time, we show that based on DNA methylation and proteome data carcinoma-related STM more closely resemble yolk-sac tumors, while sarcoma-related STM resemble teratoma. STM harbor mutations in FGF signaling factors (FGF6/23, FGFR1/4) highlighting the corresponding pathway as a therapeutic target. Furthermore, STM utilize signaling pathways, like AKT, FGF, MAPK, and WNT to mediate molecular functions coping with oxidative stress, toxin transport, DNA helicase activity, apoptosis and the cell cycle. Collectively, these data might explain the high therapy resistance of STM. Finally, we identified putative novel biomarkers secreted by STM, like EFEMP1, MIF, and DNA methylation at specific CpG dinucleotides.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Humanos , Metilação de DNA , Proteoma/genética , Proteoma/metabolismo , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/genética , Teratoma/genética , Teratoma/metabolismo , Teratoma/patologia , Biomarcadores/metabolismo , Proteínas da Matriz Extracelular/genética
17.
Hinyokika Kiyo ; 69(6): 157-162, 2023 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-37460279

RESUMO

The patient was a 27-year-old male. In December 2020, he was diagnosed with a primary extragonadal germ cell tumor of the retroperitoneum with inferior vena caval (IVC) involvement. After 3 courses of bleomycin, etoposide and cisplatinum and 3 courses of paclitaxel, ifosfamide and cisplatin, the serum human chorionic gonadotropin (hCG) level remained abnormally low. He was referred to our department after follow-up for 2 months. Since the hCG level continued to decrease during follow-up, we decided to perform marker-positive surgery. He underwent retroperitoneal lymph node dissection. We also resected a part of the IVC wall and tumor in the IVC. The serum hCG level was normalized at 5 days after surgery. Pathological examination revealed only necrotic tissue. Immunohistochemistry showed hCG positive in the necrotic tissue.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Excisão de Linfonodo , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Bleomicina/uso terapêutico , Cisplatino , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia
18.
Curr Oncol ; 30(7): 6166-6176, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37504318

RESUMO

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


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Embrionárias de Células Germinativas , Masculino , Humanos , Etoposídeo/uso terapêutico , Prognóstico , Recidiva Local de Neoplasia/tratamento farmacológico , Canadá , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico
19.
World J Urol ; 41(9): 2405-2411, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37507528

RESUMO

PURPOSE: To evaluate the feasibility, safety, and early oncologic outcomes after post-chemotherapy robot-assisted retroperitoneal lymph node dissection (PC-RARPLND) for metastatic germ cell tumors (mGCT). METHODS: We retrospectively analyzed patients from four tertiary centers who underwent PC-RARPLND for mGCT, from 2011 to 2021. Previous treatment of mGCT, intraoperative and postoperative complications, and early oncologic outcomes were assessed. RESULTS: Overall, 66 patients were included. The majority of patients had non-seminoma mTGCT (89%). Median size of retroperitoneal lymph node (RLN) before surgery was 26 mm. Templates of PC-RARPLND were left modified, right modified, and full bilateral in 56%, 27%, and 14%, respectively. Median estimated blood loss and length of stay were 50 mL [50-150] and 2 [1-3] days. Four patients (6.1%) had a vascular injury, only one with significant blood loss and conversion to open surgery (OS). Two other patients had a conversion to OS for difficulty of dissection. No patient had transfusion, most frequent complications were ileus (10.6%) and symptomatic lymphorrea (7.6%) and no complications grade IIIb or more occurred. With a median follow-up of 16 months, two patients had a relapse, all outside of the surgical template (one in the retrocrural space with reascending markers, one in lungs). CONCLUSION: PC-RARPLND is a challenging surgery. In expert centers and for selected patients, it seemed safe and feasible, with a low morbidity. Further prospective evaluation of this procedure and long-term oncologic results are needed.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Robótica , Neoplasias Testiculares , Masculino , Humanos , Estudos Retrospectivos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Testiculares/patologia , Metástase Linfática/patologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Espaço Retroperitoneal/cirurgia
20.
J Clin Oncol ; 41(23): 3899-3904, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37410968

RESUMO

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.Optimal treatment of patients with testicular germ cell tumors requires a coordinated multidisciplinary approach, so that surgery, chemotherapy, and, when appropriate, radiation therapy can be integrated into a coherent and comprehensive treatment plan. Nonseminomatous germ cell tumors (NSGCT) are often a mixture of teratoma and cancer (choriocarcinoma, embryonal carcinoma, seminoma, and/or yolk sac tumor). While the cancers are highly sensitive to and often cured by chemotherapy, teratoma is resistant to chemotherapy and radiation therapy and generally must be resected surgically to be successfully treated. Therefore, the standard of care for metastatic NSGCT is to resect all resectable residual masses after chemotherapy. If such resection reveals only teratoma and/or necrosis/fibrosis, then patients are put on a surveillance schedule to monitor for relapse. If viable cancer is found and there are positive margins or 10% or more of any of the residual masses consists of viable cancer, then two cycles of adjuvant chemotherapy should be considered.


Assuntos
Neoplasias Embrionárias de Células Germinativas , Teratoma , Neoplasias Testiculares , Masculino , Humanos , Adulto , Adolescente , Recidiva Local de Neoplasia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Teratoma/tratamento farmacológico
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