RESUMO
PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.
Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/mortalidade , Masculino , Feminino , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Administração Intravesical , Seguimentos , Idoso , Pessoa de Meia-Idade , Carcinoma in Situ/patologia , Carcinoma in Situ/terapia , Carcinoma in Situ/tratamento farmacológico , Invasividade Neoplásica , Resultado do Tratamento , Adenoviridae/genética , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode antiviral proteins, have distinctive nucleotide compositions. We propose that self-targeting by antiviral effectors has selected for ISG transcripts that occupy a less self-targeted sequence space. Following interferon (IFN) stimulation, the CpG-targeting antiviral effector zinc-finger antiviral protein (ZAP) reduces the mRNA abundance of multiple host transcripts, providing a mechanistic explanation for the repression of many (but not all) interferon-repressed genes (IRGs). Notably, IRGs tend to be relatively CpG rich. In contrast, highly upregulated ISGs tend to be strongly CpG suppressed. Thus, ZAP is an example of an effector that has not only selected compositional biases in viral genomes but also appears to have notably shaped the composition of host transcripts in the vertebrate interferome.
Assuntos
Fosfatos de Dinucleosídeos , Fatores Reguladores de Interferon/genética , RNA Viral , Proteínas de Ligação a RNA/metabolismo , Células A549 , Linhagem Celular , Humanos , Interferon beta/farmacologia , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Fenômenos Fisiológicos Virais , VírusRESUMO
BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3â×â1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.
Assuntos
Adenoviridae/genética , Vacina BCG/administração & dosagem , Carcinoma in Situ/terapia , Resistencia a Medicamentos Antineoplásicos , Terapia Genética , Vetores Genéticos , Interferon alfa-2/genética , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Vacina BCG/efeitos adversos , Carcinoma in Situ/genética , Carcinoma in Situ/mortalidade , Carcinoma in Situ/patologia , Progressão da Doença , Feminino , Terapia Genética/efeitos adversos , Terapia Genética/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Recidiva Local de Neoplasia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: To assess the use of several preoperative parameters in predicting the side of pelvic lymph node metastasis in patients with prostate cancer. MATERIALS AND METHODS: A retrospective chart review (January 1982 to February 2004) identified 106 men with pathology proven lymph node positive prostate cancer for whom complete medical records were available. RESULTS: The median serum prostate-specific antigen at diagnosis was 11 ng/ml with the clinical stage T1C in 9 patients, T2 in 68, and T3 in 29. The Gleason score on transrectal ultrasonography (TRUS) biopsy was < or =6 in 13, 7 in 41, and > or =8 in 52. A total of 93 patients had documented pretreatment digital rectal examination (DRE) findings: 54 had a unilaterally suspicious DRE, and 31 had a bilaterally suspicious DRE. Of patients with a unilaterally positive DRE, 30 had ipsilateral lymph node metastasis, 16 contralateral, and 8 bilateral. DRE showed a 71% sensitivity and 29% false-negative rate in predicting the side of nodal metastasis. A total of 98 patients had documented TRUS biopsy findings: 37 had unilaterally positive TRUS biopsies and 61 bilaterally positive biopsies. Of patients with unilaterally positive TRUS biopsies, 20 had ipsilateral lymph node metastasis, 11 contralateral, and 6 bilateral. TRUS biopsies showed an 86% sensitivity and 14% false-negative rate in predicting the side of nodal metastasis. CONCLUSIONS: DRE and TRUS biopsies do not accurately predict the side of pelvic lymph node metastasis and should not determine the extent of the pelvic lymphadenectomy.
Assuntos
Linfonodos/patologia , Exame Físico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/secundário , Adulto , Idoso , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Estudos Retrospectivos , UltrassonografiaRESUMO
PURPOSE: To identify patients who would benefit from robot-assisted radical cystectomy (RARC), we report perioperative outcomes and complications. PATIENTS AND METHODS: We compared patients who underwent RARC to patients who underwent open cystectomy (OC) in our institution. Data included demographics, operative variables, and recovery. Complications were grouped into early (<30 days), intermediate (31-90 days), and late (>90 days). RESULTS: There were 58 patients in the RARC group and 84 patients in the OC group. The mean age was 66 ± 1.2 years in the RARC v 67 ± 1.2 in OC (p=0.53) group. Women constituted 21% in the RARC and 30% in OC (p=0.23) group. The mean American Society of Anesthesiologists scores were 2.9 for the RARC and 2.94 for OC (p=0.5). The mean operative time for RARC was 7.8 ± 1.5 hours v 6.6 ± 1.25 hours for OC (p<0.0001). Estimated blood loss was 276 ± 48 mL in RARC v 1522 ± 369 mL in OC (p<0.0001). Positive margin rate was 7% in RARC v 8% in OC (p=0.8). Early complications of any severity (Clavien scores) occurred in 43% in RARC and 64% in OC (p=0.02). There was one mortality in RARC and two mortalities in OC. Patients were grouped by age (≥ 70- and <70-years old). The older group consisted of 19 and 44 patients in RARC and OC, respectively. Both age groups in RARC had less early complications than OC patients (p<0.014). The older group in RARC had less early complication rate (17%) than the younger group in OC (59%). CONCLUSIONS: RARC has improved perioperative outcomes with equivalent oncological parameters when compared to open cystectomy. Patients ≥ 70-years old benefit from the robotic approach, particularly when compared to younger patients undergoing open cystectomy.
Assuntos
Cistectomia/métodos , Laparotomia/métodos , Robótica , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação/tendências , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/cirurgiaRESUMO
OBJECTIVES: To explore the relationship between renal cell carcinoma rates and health status and behavior in the United States. METHODS: The renal cell carcinoma incidence (2003-2004) and mortality rates (2000-2003) for males and females were compared with the levels of current smokers, obesity, physical inactivity, hypertension, diabetes, high fruit/vegetable diet, and excessive alcohol consumption on a state-by-state basis. Family income, lack of health insurance, urbanization, and urologist population density among the states were included to adjust for access to healthcare and socioeconomic status. RESULTS: The renal cell carcinoma incidence and mortality rates for both males and females correlated directly with the levels of smoking, obesity, and physical inactivity. The incidence rates correlated directly with hypertension for both sexes and the urologist population density for males. The mortality rates correlated inversely with high fruit/vegetable consumption, family income, and urbanization for both sexes. Multivariate analysis identified best-fit models for predicting renal cell carcinoma rates. Physical inactivity and urologist population density were the strongest variables for predicting the incidence rates in males; smoking for predicting the incidence rates in females; and smoking and high fruit/vegetable diet for predicting mortality in both sexes. CONCLUSIONS: In the present study, we found that smoking, obesity, and physical inactivity correlated directly with the renal cell carcinoma incidence and mortality and hypertension correlated directly with the incidence rates. A high fruit/vegetable diet, family income, and urbanization correlated inversely with renal cell carcinoma mortality rates. The prevalence of urologists correlated directly with the incidence rates for males but not for females.
Assuntos
Carcinoma de Células Renais/epidemiologia , Comportamentos Relacionados com a Saúde , Nível de Saúde , Neoplasias Renais/epidemiologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Incidência , Neoplasias Renais/complicações , Neoplasias Renais/mortalidade , Masculino , Atividade Motora , Obesidade/complicações , Fumar , Estados Unidos/epidemiologiaRESUMO
PURPOSE: We assessed the sensitivity of preoperative lymphoscintigraphy and dynamic sentinel node biopsy for staging the inguinal region of patients with penile cancer and no palpable inguinal adenopathy. MATERIALS AND METHODS: The records of 31 patients with invasive penile cancer and nonpalpable (29) or nonsuspicious (2) inguinal lymph nodes were reviewed. Preoperatively lymphoscintigraphy plus dynamic sentinel node biopsy with (99m)technetium labeled sulfur colloid and isosulfan blue dye was performed in 21 patients and dynamic sentinel node biopsy alone with blue dye only was done in 10. All patients underwent superficial lymph node dissection regardless of preoperative lymphoscintigraphy or dynamic sentinel node biopsy findings to establish pathological nodal status. RESULTS: Six of 32 groins that showed drainage on preoperative lymphoscintigraphy had inguinal node metastasis, as did 1 of 10 that was drainage negative. The sensitivity of preoperative lymphoscintigraphy drainage for cancer detection was 86%. Using dynamic sentinel node biopsy with blue dye plus radiotracer 5 sentinel lymph nodes were positive for cancer, although 2 false-negative results were obtained. Thus, the sensitivity of dynamic sentinel node biopsy per groin for cancer detection was 71%. CONCLUSIONS: In our experience preoperative lymphoscintigraphy and dynamic sentinel node biopsy as currently performed remain insufficient for detecting occult inguinal disease. Superficial lymph node dissection remains the gold standard for detecting inguinal microscopic metastasis in select patients.
Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Estadiamento de Neoplasias/métodos , Neoplasias Penianas/diagnóstico por imagem , Neoplasias Penianas/patologia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/cirurgia , Corantes , Humanos , Canal Inguinal , Masculino , Pessoa de Meia-Idade , Neoplasias Penianas/cirurgia , Estudos Prospectivos , Cintilografia , Compostos Radiofarmacêuticos , Corantes de Rosanilina , Sensibilidade e Especificidade , Coloide de Enxofre Marcado com Tecnécio Tc 99mRESUMO
BACKGROUND: The current study was conducted to determine the clinical characteristics and prognostic features associated with prostatic small cell carcinoma (SCC). METHODS: Between January 1985 and May 2005, 83 patients with SCC of the prostate were identified. Univariate and multivariate Cox proportional hazards modeling were used to assess the prognostic significance of the clinical parameters associated with disease-specific outcomes. RESULTS: Twenty-one patients had no evidence of distant metastasis at the time of the diagnosis of SCC, with the remaining patients demonstrating radiologic or biopsy-proven evidence of metastatic disease. Compared with patients with metastases, patients without metastases at the time of diagnosis were older (P = .001) and had a lower serum lactate dehydrogenase (LDH) level at the time of diagnosis (P = .002). On multivariate analysis, an elevated serum LDH level and low serum albumin at the time of SCC diagnosis was found to be predictive of inferior progression-free survival (P = .02 and P = .008, respectively) and inferior disease-specific survival (DSS) (P = .02 and P = .01, respectively). At the time of last follow-up, 72 patients (87%) had died of disease, with a median DSS duration of 13.1 months (range, 10.7-17.1 months). There was a statistically significant difference noted with regard to the median DSS of patients with nonmetastatic versus those with metastatic SCC (17.7 months [95% confidence interval (95% CI), 12.1-39.2 months] vs 12.5 months [95% CI, 8.1-16.1 months], respectively; P = .03). CONCLUSIONS: SCC of the prostate is a highly aggressive tumor, with serum LDH and albumin levels at the time of diagnosis believed to be predictive of disease-related outcomes. Although palliative, current systemic therapy does not result in cure and does not provide long-term survival for patients with metastases. For patients with nonmetastatic disease, a strategy utilizing systemic and local therapies should be evaluated further.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Carcinoma de Células Pequenas/terapia , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Terapia Combinada , Intervalo Livre de Doença , Humanos , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Albumina Sérica/análise , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To review our experience with the surgical management of lymph node-positive prostate cancer and to determine if there is a benefit to treating such patients with immediate rather than delayed hormonal therapy (HT). PATIENTS AND METHODS: A retrospective analysis from January 1982 to January 2001 identified 100 patients treated by radical retropubic prostatectomy (RP) either alone (70, 23 later received delayed HT) or combined with adjuvant (immediate) HT (30), with the overall median follow-up being 5.2 years. RESULTS: The median patient age at diagnosis was 58.7 years, with 20% having clinical T3 disease, and the median prostate specific antigen (PSA) level at presentation was 10 ng/mL. In 41% of patients the Gleason score on prostatic biopsy was > or = 8. After RP, 30 patients received immediate HT used as an adjuvant after surgery in the absence of any evidence of disease progression, whereas 23 received delayed HT the use of which was provoked secondary to biochemical failure (PSA threshold of 0.2-5.0 ng/mL) with no evidence of metastatic disease. A comparison of the clinical variables between the groups showed a higher median PSA level at diagnosis (P = 0.027) and biopsy Gleason score (P = 0.052) in the delayed HT group. The immediate and delayed HT groups had similar metastatic-free (P = 0.549), disease-specific (P = 0.843) and overall survival (P = 0.843). Overall, biochemical failure developed in half the patients and distant metastasis in 13%, with only nine patients dying from disease. CONCLUSIONS: Immediate and delayed HT provide similar treatment outcomes in patients with surgically managed lymph node-positive prostate cancer.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoAssuntos
Política de Saúde/economia , Transição Epidemiológica , Neoplasias da Próstata/economia , Neoplasias da Próstata/terapia , Qualidade da Assistência à Saúde/economia , Humanos , Masculino , Neoplasias da Próstata/mortalidade , Qualidade da Assistência à Saúde/normas , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Inhibiting phosphorylation of platelet-derived growth factor receptor (PDGFR) by treatment with the PDGFR kinase inhibitor imatinib and the chemotherapeutic agent paclitaxel reduces the incidence and size of human prostate cancer bone lesions in nude mice. Because tumor cells and tumor-associated endothelial cells express activated PDGFR, the primary target for imatinib has been unclear. METHODS: We selected multidrug-resistant human PC-3MM2 prostate cancer cells (termed PC-3MM2-MDR cells) by culturing them in increasing concentrations of paclitaxel. PC-3MM2-MDR cells were implanted into one tibia of 80 nude mice. Two weeks later, the mice were randomly assigned to receive distilled water (control group), paclitaxel, imatinib, or imatinib plus paclitaxel for 10 weeks (20 mice per group). Tumor incidence and weight, bone structure preservation and osteolysis, and the incidence of lymph node metastasis were determined. The phosphorylation status of PDGFR on tumor cells and tumor-associated endothelial cells and levels of apoptosis were examined with immunohistochemical analyses. Microvessel density was assessed as the number of cells expressing CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1). All statistical tests were two-sided. RESULTS: PC-3MM2-MDR cells were resistant to paclitaxel and imatinib in vitro. Treatment of implanted mice with imatinib plus paclitaxel led to statistically significant decreases in bone tumor incidence (control = 19 mice with tumors of 19 mice total; imatinib plus paclitaxel = four of 18 mice; P < .001), median tumor weight (control = 1.3 g, interquartile range [IQR] = 1.0-1.9; imatinib plus paclitaxel = 0.1 g, IQR = 0-0.3; P < .001), bone lysis, and the incidence of lymph node metastasis (control = 19 of 19 mice total; imatinib plus paclitaxel = three of 18 mice; P < .001). Treatment with imatinib alone had similar effects, and imatinib treatment also inhibited phosphorylation of PDGFR on tumor cells and tumor-associated endothelial cells and increased the level of apoptosis of endothelial cells, but not tumor cells. Treatment with imatinib and more so with imatinib and paclitaxel decreased mean vessel density (three CD31/PECAM-1-positive cells, 95% confidence interval [CI] = 0 to 9; and control group = 38 CD31/PECAM-1-positive cells, 95% CI = 17 to 59) (P < .001), which was followed by apoptosis of tumor cells. CONCLUSION: Tumor-associated endothelial cells, rather than tumor cells themselves, appear to be the target for imatinib in prostate cancer bone metastasis.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Células Endoteliais/efeitos dos fármacos , Paclitaxel/farmacologia , Piperazinas/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Pirimidinas/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Benzamidas , Western Blotting , Neoplasias Ósseas/irrigação sanguínea , Neoplasias Ósseas/química , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Células Endoteliais/metabolismo , Imunofluorescência , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Metástase Linfática/prevenção & controle , Masculino , Camundongos , Camundongos Nus , Microcirculação/efeitos dos fármacos , Transplante de Neoplasias , Neovascularização Patológica/prevenção & controle , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Distribuição Aleatória , Receptores do Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tíbia/efeitos dos fármacos , Tíbia/patologia , Células Tumorais CultivadasRESUMO
Boys with Klinefelter's syndrome are at an increased risk of precocious puberty. Most cases are either idiopathic or due to a mediastinal tumor. Patients with Klinefelter's syndrome are at a high risk of primary, extragonadal germ cell tumors, which are usually nonseminomatous, but can be a mixed type with seminomatous elements. The differential diagnosis of precocious puberty includes mediastinal tumors, especially in boys with Klinefelter's syndrome.