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1.
J Pediatr Hematol Oncol ; 46(5): e313-e316, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857191

RESUMO

In the most recent fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System, astroblastoma has been defined by molecular rearrangements involving the MN1 gene, with common partners being BEND2 or CXXC5 . Accordingly, this tumor entity is now known as "astroblastoma, MN1 -altered." However, gliomas with EWSR1::BEND2 fusions, devoid of MN1 fusion alterations, have recently been shown to exhibit astroblastoma-like histomorphologic features and reside in a distinct epigenetic subgroup based on DNA methylation studies similar to high-grade neuroepithelial tumor with MN1 alteration, which includes astroblastoma, MN1 altered tumors. This new epigenetically distinct subtype of astroblastoma containing EWSR1::BEND2 fusions lacks the required MN1 alteration and, thus, does not satisfy the current molecular classification of these lesions. Here, we describe a case of glioma with histologic features and DNA methylation profiling consistent with astroblastoma with a novel YAP1: : BEND2 fusion. This case and others further expand the molecular findings observable in astroblastoma-like tumors outside the constraints of MN1 alteration. Such cases of astroblastoma with EWSR1::BEND2 and YAP1::BEND2 fusions challenge the current molecular classification of astroblastoma based solely on an MN1 alteration.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Neuroepiteliomatosas , Proteínas de Fusão Oncogênica , Fatores de Transcrição , Proteínas de Sinalização YAP , Humanos , Neoplasias Neuroepiteliomatosas/genética , Neoplasias Neuroepiteliomatosas/patologia , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Masculino , Metilação de DNA , Fosfoproteínas/genética , Feminino
2.
Lung Cancer ; 184: 107352, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37657238

RESUMO

OBJECTIVES: About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking. MATERIALS AND METHODS: We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort. RESULTS: We found sixteen nonsynonymous mutations harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22-26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182, miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients. CONCLUSION: Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , MicroRNAs , Humanos , Sequenciamento do Exoma , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/genética , MicroRNAs/genética , Receptores ErbB/genética
3.
Oncol Lett ; 26(1): 284, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37274483

RESUMO

Patients with high-risk prostate cancer after prostatectomy have a particularly high chance of being diagnosed with biochemical recurrence (BCR). Patients with BCR have a greater risk of disease progression and mortality. The present retrospective observational study aimed to clarify the risk factors for the BCR of prostate cancer after radical prostatectomy in patients with high-risk and very high-risk prostate cancer. Patients diagnosed with prostate cancer who received radical prostatectomy in a single center from January 2009 to June 2020 were included in the study. Data from medical records were reviewed and the patients were followed up for ≥6 years. The primary outcome was BCR within 1 year after surgery. A total of 307 patients were included, with 187 in the high-risk group and 120 in the very high-risk group as classified by the National Comprehensive Cancer Network (NCCN) guidelines. Patients in the very high-risk group had a lower BCR-free survival rate compared with those in the high-risk group, with a high risk of BCR even if their PSA levels were initially undetectable after prostatectomy, and a high risk of postoperatively detectable PSA. In patients with undetectable PSA after prostatectomy, BCR was associated with the initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1). Postoperatively detectable PSA was associated with pathologic stage (T3bN0M0 and any N1) In conclusion, preoperative MRI imaging stage and PSA density are predictors for short-term BCR after prostatectomy. NCCN-defined high-risk patients with a high initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1) had a higher risk of BCR when compared with other patients with undetectable PSA, while those with pathologic stage (T3bN0M0 or any N1) displayed a higher risk of postoperatively detectable PSA. These findings may help urologists to identify patients for whom active therapeutic protocols are necessary.

4.
Biomed Res Int ; 2022: 2832996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303584

RESUMO

Purpose: A non-invasive way of assessing post-transplant renal graft function has been needed. This study aimed to assess the micro-structural and micro-functional status of graft kidneys by using intravoxel incoherent motion- (IVIM-) diffusion-weighted imaging (DWI) to investigate delayed graft function (DGF) immediately after transplantation. Method: A prospective study was conducted on 37 patients, 14 with early graft function (EGF) and 23 with DGF (9 with complication, 14 without) who underwent IVIM-DWI, most often within 1-7 days after kidney transplantation. A total of 37 cases were collected and all the participants have been well-informed and signed their consents. In addition, the study conducted in this paper was approved by the Ethics Committee of Clinical Research, Taichung Veterans General Hospital (IRB number: CE14065). Using biexponential analysis of slow diffusion coefficient (D slow), fast diffusion coefficient (D fast), and perfusion fraction was performed. The apparent diffusion coefficient (ADC) was calculated by use of a monoexponential model. All parameters were measured from three different regions-of-interest (ROI), covering the entire renal parenchyma, cortex, and medulla. Results: D slow, perfusion fraction, and ADC were significantly higher in patients with EGF than DGF (all p values values <0.001). Especially, ADC measured from ROI covering the entire kidney parenchyma had the best cut-off value (1.93µm2/msec) with the highest area under the receiver operating characteristic curve (AUC 0.943) in differentiating EGF from DGF. For analysis of pair-wise differences, only the perfusion fraction values, measured from the ROI covering the renal cortex, were significantly higher in 14 DGF patients with no complications than in the 9 DGF patients with complications, with the best cut-off value of 12.3% and the AUC of 0.844. Conclusion: Noninvasive IVIM-DWI reliably differentiates DGF from EGF after kidney transplantation, and it may aid in identifying posttransplant complications and indications for renal biopsy.


Assuntos
Transplante de Rim , Humanos , Função Retardada do Enxerto/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Transplante de Rim/efeitos adversos , Estudos Prospectivos
5.
Int J Urol ; 29(1): 69-75, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34608678

RESUMO

OBJECTIVES: To investigate the significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. METHODS: Between January 2001 and December 2015, 548 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy in a single institution were included in this retrospective cohort study. Several clinicopathological characteristics and outcomes were explored. The crucial end-point was the diagnosis of contralateral upper tract recurrence after radical nephroureterectomy. RESULTS: Of the 548 patients, the median age was 68 years (range 24-93 years), and the median follow-up time after radical nephroureterectomy was 41 months (range 8-191 months). Contralateral upper tract recurrence occurred in 28 patients (5.1%). The median time period between radical nephroureterectomy and contralateral upper tract recurrence was 15.4 months (range 3.4-52.4 months). In the multivariate analysis, preoperative estimated glomerular filtration rate <30 mL/min/1.73 m2 (hazard ratio 3.08, P = 0.003) and tumor multifocality (hazard ratio 2.16, P = 0.043) were independent risk factors. CONCLUSION: Preoperative estimated glomerular filtration rate <30 and tumor multifocality are significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.


Assuntos
Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/cirurgia , Taxa de Filtração Glomerular , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Nefroureterectomia , Estudos Retrospectivos , Neoplasias Ureterais/epidemiologia , Neoplasias Ureterais/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Adulto Jovem
6.
Theranostics ; 11(19): 9667-9686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646392

RESUMO

The tumorous niche may drive the plasticity of heterogeneity and cancer stemness, leading to drug resistance and metastasis, which is the main reason of treatment failure in most cancer patients. The aim of this study was to establish a tumor microenvironment (TME)-based screening to identify drugs that can specifically target cancer stem cells (CSCs) and cancer-associated fibroblasts (CAFs) in the TME. Methods: Lung cancer patient-derived cancer cell and CAFs were utilized to mimic the TME and reproduce the stemness properties of CSCs in vitro and develop a high-throughput drug screening platform with phenotypical parameters. Limiting dilution assay, sphere-forming and ALDH activity assay were utilized to measure the cancer stemness characteristics. In vivo patient-derived xenograft (PDX) models and single-cell RNA sequencing were used to evaluate the mechanisms of the compounds in CSCs and CAFs. Results: The TME-based drug screening platform could comprehensively evaluate the response of cancer cells, CSCs and CAFs to different treatments. Among the 1,524 compounds tested, several drugs were identified to have anti-CAFs, anticancer and anti-CSCs activities. Aloe-emodin and digoxin both show anticancer and anti-CSCs activity in vitro and in vivo, which was further confirmed in the lung cancer PDX model. The combination of digoxin and chemotherapy improved therapeutic efficacy. The single-cell transcriptomics analysis revealed that digoxin could suppress the CSCs subpopulation in CAFs-cocultured cancer cells and cytokine production in CAFs. Conclusions: The TME-based drug screening platform provides a tool to identify and repurpose compounds targeting cancer cells, CSCs and CAFs, which may accelerate drug development and therapeutic application for lung cancer patients.


Assuntos
Reposicionamento de Medicamentos/métodos , Células-Tronco Neoplásicas/efeitos dos fármacos , Microambiente Tumoral/fisiologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Proliferação de Células , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Detecção Precoce de Câncer , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/metabolismo , Preparações Farmacêuticas
7.
J Clin Invest ; 131(16)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34228648

RESUMO

Unlike the better-studied aberrant epigenome in the tumor, the clinicopathologic impact of DNA methylation in the tumor microenvironment (TME), especially the contribution from cancer-associated fibroblasts (CAFs), remains elusive. CAFs exhibit profound patient-to-patient tumorigenic heterogeneity. We asked whether such heterogeneity may be exploited to quantify the level of TME malignancy. We developed a robust and efficient methylome/transcriptome co-analytical system for CAFs and paired normal fibroblasts (NFs) from non-small-cell lung cancer patients. We found 14,781 CpG sites of CAF/NF differential methylation, of which 3,707 sites showed higher methylation changes in ever-smokers than in nonsmokers. Concomitant CAF/NF differential gene expression analysis pointed to a subset of 54 smoking-associated CpG sites with strong methylation-regulated gene expression. A methylation index that summarizes the ß values of these CpGs was built for NF/CAF discrimination (MIND) with high sensitivity and specificity. The potential of MIND in detecting premalignancy across individual patients was shown. MIND succeeded in predicting tumor recurrence in multiple lung cancer cohorts without reliance on patient survival data, suggesting that the malignancy level of TME may be effectively graded by this index. Precision TME grading may provide additional pathological information to guide cancer prognosis and open up more options in personalized medicine.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Epigenoma , Neoplasias Pulmonares/genética , Fumar/efeitos adversos , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibroblastos Associados a Câncer/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ilhas de CpG , Metilação de DNA , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Fumar/genética , Fumar/metabolismo , Células Tumorais Cultivadas , Microambiente Tumoral/genética
8.
Diagnostics (Basel) ; 10(4)2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32260187

RESUMO

The purpose of this study was to identify the significant risk factors of urinary bladder recurrence (UBR) after nephroureterectomy (NUx) in patients with upper tract urothelial carcinoma (UTUC). A total of 550 patients diagnosed with UTUC between January 2001 and December 2015 were included in this retrospective study. The median age of our patients was 68 (range 24-93) and the median follow-up time after NUx was 40.3 months (range 8-191). The most important censored point of this study was the first episode of UBR. Of the 550 patients, UBR occurred in 164 patients (29.8%). One hundred and forty-two (86.6%) patients with UBR were identified within two years after NUx for UTUC, with the median time interval between NUx and UBR being 8.4 months (range 3-59.8). Through univariate analysis, the positive surgical margin (p = 0.049) and tumor multifocality (p = 0.024) were both significant prognostic factors for UBR-free survival after NUx in patients with UTUC. However, only tumor multifocality (p = 0.037) remained a significant prognostic factor by multivariate analysis. In conclusion, tumor multifocality is a significant risk factor of UBR after nephroureterectomy in patients with upper tract urothelial carcinoma.

9.
BMC Nephrol ; 21(1): 6, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906890

RESUMO

BACKGROUND: Chronic active antibody-mediated rejection is a major etiology of graft loss in renal transplant recipients. However, there is no consensus on the optimal treatment strategies. METHODS: Computerized records from Taichung Veterans General Hospital were collected to identify renal transplant biopsies performed in the past 7 years with a diagnosis of chronic active antibody-mediated rejection. The patients were divided into two groups according to treatment strategy: Group 1 received aggressive treatment (double filtration plasmapheresis and one of the followings: rituximab, intravenous immunoglobulin, antithymogycte globulin, bortezomib, or methylprednisolone pulse therapy); and group 2 received supportive treatment. RESULTS: From February 2009 to December 2017, a total of 82 patients with biopsy-proven chronic antibody mediated rejection were identified. Kaplan-Meier analysis of death-censored graft survival showed a worse survival in group 2 (P = 0.015 by log-rank test). Adverse event-free survival was lower in group 1, whereas patient survival was not significantly different. Proteinuria and supportive treatment were independent risk factors for graft loss in multivariate analysis. CONCLUSIONS: Aggressive treatment was associated with better graft outcome. However, higher incidence of adverse events merit personalized treatment, especially for those with higher risk of infection. Appropriate prophylactic antibiotics are recommended for patients undergoing aggressive treatment.


Assuntos
Rejeição de Enxerto/imunologia , Fatores Imunológicos/uso terapêutico , Transplante de Rim , Rim/patologia , Adulto , Antibacterianos/uso terapêutico , Anticorpos , Soro Antilinfocitário/uso terapêutico , Biópsia , Bortezomib/uso terapêutico , Terapia Combinada , Rejeição de Enxerto/patologia , Rejeição de Enxerto/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Transplante de Rim/mortalidade , Pessoa de Meia-Idade , Plasmaferese , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Rituximab/uso terapêutico , Análise de Sobrevida
10.
Asian J Surg ; 43(1): 257-264, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31324510

RESUMO

BACKGROUND/OBJECTIVES: To investigate the oncological and functional outcomes after partial nephrectomy for clinical stage T1 (cT1) renal cell carcinoma (RCC), and assess the association between excisional volume loss (EVL) and postoperative renal function. METHODS: We retrospectively reviewed 150 patients with cT1 RCC undergoing partial nephrectomy from 2002 to 2016. End-point evaluation was assessed by recurrence free survival (RFS), overall survival (OS), stage III and stage IV chronic kidney disease (CKD). Regression models were used to determine the risk factors of CKD after surgery. The relationship between EVL and renal function decline was evaluated using Spearman correlation method. RESULTS: Ninety patients with clinical stage T1a (cT1a) tumors and 60 patients with clinical stage T1b (cT1b) tumors were included. There were no differences in RFS, OS, and risk of stage III and stage IV CKD between the two groups. In Cox regression models, multivariate analysis showed that preoperative estimated glomerular filtration rate (eGFR) was an independent risk factor for developing stage III (hazard ratio 0.937, P < 0.001) and stage IV CKD (hazard ratio 0.929, P = 0.027). EVL was significantly associated with postoperative eGFR decrease. (Correlation Coefficient = 0.325, P = 0.003). CONCLUSIONS: Patients with cT1a and cT1b RCC have comparable oncological and functional outcome after partial nephrectomy, and preoperative eGFR is an independent factor to predict developing CKD. EVL has influence on the postoperative renal function decline.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Carcinoma de Células Renais/cirurgia , Testes de Função Renal , Neoplasias Renais/fisiopatologia , Neoplasias Renais/cirurgia , Rim/patologia , Rim/cirurgia , Nefrectomia/métodos , Recuperação de Função Fisiológica , Adulto , Idoso , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
11.
Anticancer Res ; 39(7): 3901-3908, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262919

RESUMO

BACKGROUND/AIM: Abiraterone (AA) and enzalutamide (ENZ) were introduced in Taiwan since 2012 for the treatment of patients with post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). This study aims to retrospectively compare the efficacy of the two regimens. MATERIALS AND METHODS: The study cohort consisted of 77 mCRPC patients previously treated with docetaxel and subsequently with AA (n=63, the AA group) or ENZ (n=13, the ENZ group), all treated in our hospital. Clinical parameters of the two groups were compared to determine differences between pre-treatment variables and treatment outcomes. RESULTS: Sixty-four patients received AA and 13 received ENZ, with a median 18.2 vs. 14.5 months follow-up (p=0.434). Prostate-specific antigen (PSA) response >50% was 31 (48.4%) in AA and 9 (69.2%) in ENZ (p=0.171), while PSA response >90% was 16 (25%) in AA and 5 (38.5%) in ENZ (p=0.32). The median progression-free survival (PFS) was 7.3 (95%CI=4.796-9.804) months in AA and 9.5 months (95%CI=5.743-13.257) in ENZ (p of log rank=0.766). The median overall survival (OS) from second-line hormone treatment was 30.2 months in AA group and 16.2 months in ENZ group (p of log rank=0.734). Neither the uni- nor the multi-variate COX-regression analysis distinguished any advantage of the two-drug regimen in terms of PFS or OS. Metastasis volume (HR=3.032, 95%CI=1.281-7.178, p=0.012) and nadir PSA (HR=1.000, 95%CI=1.000-1.001, p=0.010) were shown as independent risk factors for the survival of AA/ENZ-treated patients. CONCLUSION: AA and ENZ had a similar efficacy in treating post-docetaxel mCRPC patients. Metastatic volume and nadir PSA were independent risk factors of these patients in predicting their disease-specific survival and overall survival.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antineoplásicos/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Benzamidas , Docetaxel/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
12.
Biofactors ; 45(1): 62-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30334297

RESUMO

Fibroblast growth factors (FGF) 19, 21, and 23 have been reported as functional factors in human metabolic diseases and malignancies. We performed a prospective survey to compare circulating FGF levels in urothelial carcinoma (UC) patients and normal controls. Between 2016 and 2017, 39 patients with UC of the urinary bladder or upper urinary tract who received surgical intervention were included. All the serum samples were obtained before surgeries. The control group included 28 healthy volunteers. Analysis of the circulating FGF19, 21, and 23 levels among all 67 subjects, as well as a subgroup analysis of the 39 UC patients were performed. The median levels of serum FGF19, 21, and 23 in the UC patients were 84.2, 505.3, and 117.6 pg/mL, respectively, which were statistically different from levels found in the healthy controls (P = 0.015, <0.001 and < 0.001, respectively). In the subgroup analysis, the FGF19 and FGF21 levels were significantly higher in end-stage renal disease UC patients, while FGF21 was also higher in the UC patients with cardiovascular diseases and history of recurrent UC. In the receiver operating characteristic (ROC) curve analysis, FGF19, 21, and 23 were all significant predictors of UC [area under the curve (AUC)] 0.674, P = 0.015; AUC 0.918, P < 0.001; AUC 0.897, P < 0.001, respectively). In UC patients, serum FGF19 level was significantly lower, while FGF21 and 23 were significantly higher, than respective levels in healthy controls. All three markers may serve as good predictors of UC occurrence, and FGF21 level was associated with disease recurrence. © 2018 BioFactors, 45(1):62-68, 2019.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Fatores de Crescimento de Fibroblastos/genética , Neoplasias Ureterais/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/sangue , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma/cirurgia , Estudos de Casos e Controles , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Recidiva , Sensibilidade e Especificidade , Ureter/metabolismo , Ureter/patologia , Ureter/cirurgia , Neoplasias Ureterais/sangue , Neoplasias Ureterais/diagnóstico , Neoplasias Ureterais/cirurgia , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/cirurgia
13.
Int J Med Sci ; 15(14): 1731-1736, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588197

RESUMO

The high mobility group box 1 gene (HMGB1) plays a prominent role in cancer progression, angiogenesis, invasion, and metastasis. This study explored the effect of HMGB1 polymorphisms on clinicopathological characteristics of urothelial cell carcinoma (UCC). In total, 1293 participants (431 patients with UCC and 862 healthy controls) were recruited. Four single-nucleotide polymorphisms (SNPs) of HMGB1 (rs1412125, rs1360485, rs1045411, and rs2249825) were assessed using TaqMan real-time polymerase chain reaction assay. The results indicated that individuals carrying at least one T allele at rs1045411 had a lower risk of UCC than those with the wild-type allele [adjusted odds ratio = 0.722, 95% confidence interval (CI) = 0.565-0.924]. Furthermore, female patients with UCC carrying at least one T allele at rs1045411 were at a lower invasive tumor stage than those with the wild-type allele [odds ratio (OR) = 0.396, 95% CI = 0.169-0.929], similar to nonsmoking patients (OR = 0.607, 95% CI = 0.374-0.985). In conclusion, this is the first report on correlation between HMGB1 polymorphisms and UCC risk. Individuals carrying at least one T allele at rs1045411 are associated with a lower risk of UCC and a less invasive disease in women and nonsmokers.


Assuntos
Carcinoma de Células de Transição/genética , Predisposição Genética para Doença , Proteína HMGB1/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Alelos , Carcinoma de Células de Transição/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , não Fumantes , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
15.
Anticancer Res ; 38(9): 5339-5345, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30194186

RESUMO

BACKGROUND/AIM: We performed a retrospective survey on our metastatic renal cell carcinoma (MRCC) patients who had received targeted therapies, and afterwards evaluated the clinical impacts of local interventions on the patient outcomes. MATERIALS AND METHODS: Between 2006 and 2016, 124 patients with MRCC who had received at least one line of tyrosine kinase inhibitors or mammalian target of rapamycin were included in the study. Seventy-five patients (60.5%) received targeted therapies only, twenty-six patients received complete resection and the remaining 23 received incomplete local interventions for their metastatic lesions. Analysis of the basic characteristics, overall survival and multi-variant regression amongst the three groups was performed. RESULTS: The age, gender distribution, tumor cell type, targeted therapy selection, line of therapies and sites of metastases were not different amongst the three groups. The targeted therapy-only group had a significantly higher percentage of Memorial Sloan Kettering Cancer Center (MSKCC) poor-risk patients compared with the other two groups (22.7% vs. 3.8% and 0%, p=0.006 respectively). The targeted treatment duration and follow-up duration was significantly shorted in the targeted therapy-only group. Of the twelve variables analyzed, complete resection and MSKCC poor-risk group showed a significant impact on the overall survival rate (HR=0.5, 95%CI=0.25-0.98, p=0.045; HR=2.97, 95%CI=1.05-8.4, p=0.04 respectively). CONCLUSION: Complete resection of metastatic sites for MRCC patients, combined with targeted therapy, could provide better overall survival rates than targeted therapy alone. Poor MSKCC risk is still correlated to a poor outcome in the current targeted therapy era.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Metastasectomia , Terapia de Alvo Molecular , Nefrectomia , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Distribuição de Qui-Quadrado , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/enzimologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Metastasectomia/efeitos adversos , Metastasectomia/mortalidade , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/mortalidade , Análise Multivariada , Nefrectomia/efeitos adversos , Nefrectomia/mortalidade , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Taiwan , Fatores de Tempo , Resultado do Tratamento
16.
Anticancer Res ; 38(9): 5429-5436, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30194199

RESUMO

BACKGROUND/AIM: The main purpose of this study was to evaluate the outcome of patients with prostate-specific antigen (PSA) progression after abiraterone acetate (AA) treatment for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Between 2012 and 2017, 83 patients with clinically-confirmed mCRPC previously treated with docetaxel with/without cabazitaxel followed by AA were included in this retrospective study. All patients received 1,000 mg AA with 5 or 10 mg prednisolone. Among them, 59 were eligible for this study based on PSA progression during the clinical course. Patients were divided into two groups, AA responders and AA non-responders according to previous PSA response to AA treatment. Overall survival and treatment response to subsequent therapy were analyzed. RESULTS: The median overall survival of the 59 patients after AA-treated PSA progression was 12 (95% confidence interval(CI)=7.6-16.4) months and was longer in the AA-responding group compared to the non-responding group (25 vs. 8 months, p<0.001). The survival time after PSA progression on AA was longer in the AA-responsive group despite not being statistically different (13 vs. 7 months, p=0.126). Patients with AA treatment who received subsequent therapies after PSA progression had better overall survival than those without (18 vs. 4 months, p=0.003). In addition, there was a trend for better chemotherapy response in AA non-responders than AA responders, 62.5% (5/8) vs. 12.5% (1/8) respectively. CONCLUSION: In our small retrospective patient experience, effective sequential treatments for patients with mCRPC provided overall survival benefit. Previous treatment response can act as a clinical predictor for subsequent treatment.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Idoso , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos/efeitos adversos , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Regulação para Cima
17.
J Endourol ; 32(6): 502-508, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29630389

RESUMO

INTRODUCTION: A laparoscope provides many advantages when establishing abdominal access for peritoneal dialysis (PD), particularly with direct observation and correction of the catheter's position. However, laparoscopic placement requires specialized equipment and usually requires using more than one working port, which may increase the potential for complications, including dialysis leakage. We modified the surgical technique by using a nephroscope, rather than a laparoscope. This study aimed to illustrate this modified technique step by step and compare the postoperative outcomes. MATERIALS AND METHODS: This study was based on a retrospective chart review of 397 consecutive patients who underwent either laparoscope- or nephroscope-assisted PD catheter insertion between September 2005 and December 2016 in our institute, as performed by a single surgeon. Data were collected and analyzed to compare the characteristics of the patients, including age and gender, along with surgical outcomes and complications between the two groups. RESULTS: Two-hundred fourteen patients underwent laparoscopy implantation, whereas 183 patients received the nephroscope-assisted method. More patients had previously undergone abdominal surgery in the nephroscopy group (29% vs 18.7%, p = 0.035) than those in the laparoscopy group. There was no significant difference in the 1-year catheter survival (82.5% vs 79.4%, p = 0.734) rate between the two groups. A total of five patients experienced dialysis leakage within the laparoscopy group, whereas none had dialysis leakage in the nephroscopy group. CONCLUSIONS: The surgical times were significantly shorter in the nephroscopy group. Although comparison of the complication rate between the two groups revealed no statistical significance, there were trends that showed there were less early surgical complications in the nephroscopy group.


Assuntos
Cateterismo/métodos , Cateteres de Demora , Laparoscópios , Laparoscopia/métodos , Diálise Peritoneal/métodos , Adulto , Feminino , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Peritônio/cirurgia , Análise de Regressão , Estudos Retrospectivos
18.
Asian J Surg ; 41(2): 187-191, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27955873

RESUMO

BACKGROUND/OBJECTIVE: To present the long-term result and efficacy of robotic partial nephrectomy (RPN) for renal angiomyolipomas (AMLs) with perioperative outcome and renal function preservation. METHODS: From September 2006 to October 2014, the database of a single medical center was reviewed and patients who underwent RPN for AMLs were enrolled. The patient demographics, perioperative complications, and postoperative outcomes were analyzed. RESULTS: We identified 23 patients who were treated with RPN for renal AMLs. The average age was 52.7 (± 9.9) years, and 20 (87%) patients were female. The median size of the resected AML was 5.2 [interquartile range (IQR)=3.1-6.8] cm. The median estimated blood loss was 100 (IQR=50-225) mL, and three (13%) patients required blood transfusion. Perioperative complications occurred in six (26%) patients and none of them are higher than Clavien Grade II. The median estimated glomerular filtration rate at 3-month and the latest follow-ups were 103 (IQR=85.5-112) mL/min/1.73m2 and 104 (IQR=90-112) mL/min/1.73m2, respectively, with a median of 89.6% (IQR=84.2-100) and 86.9% (IQR=81.3-97.8) preservation, respectively. The median follow-up period was 40 (IQR=30.5-61.5) months. None of the patients developed complications requiring a second intervention or local recurrence of AML. CONCLUSION: A long-term follow-up of RPN for renal AMLs revealed good preservation of renal function with a low complication rate. It may be considered as a reliable method to manage renal AMLs.


Assuntos
Angiolipoma/patologia , Angiolipoma/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Angiolipoma/mortalidade , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Estudos Retrospectivos , Medição de Risco , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Taxa de Sobrevida , Taiwan , Fatores de Tempo , Resultado do Tratamento
19.
Front Pharmacol ; 8: 836, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29213237

RESUMO

Introduction: Conventional anti-androgen regimens were widely used as an initiation or combined androgen blockade (CAB) therapy in advanced prostate cancer patients. Currently, new androgen pathway inhibitors such as abiraterone acetate (AA) and enzalutamide had been proven effective in metastatic castration resistant prostate cancer. In this study, we attempt to analyze the role of conventional anti-androgen drugs as deferred CAB therapy in castration-resistant prostate cancer patients. Materials and Methods: From 2012 to 2017, 48 metastatic castration-resistant prostate cancer (CRPC) patients who received sequential treatments with primary androgen blockade, oral anti-androgen regimens, and docetaxel followed by AA treatment were included. We defined effective deferred CAB as any decline of PSA after add-on antiandrogen after CRPC. Patients were separated into effective and ineffective deferred CAB. Comparison between two groups in the first line androgen deprivation therapy duration, CRPC PSA level, pre-AA PSA level, chemotherapy dosages, duration, and patients progression free survival and overall survival after AA treatment were analyzed. Results: Twenty-three patients (47.9%) achieved PSA decline after deferred CAB. Among total 48 patients, 24 patients experienced PSA decline more than 50% after AA treatment. The median PSA progression-free survival and overall survival after AA treatment in the total cohort of 48 patients were 4.4 and 24.3 months, respectively. The effective deferred CAB group showed significantly lower PSA level, lower percentage of PSA progression, higher total follow-up duration, higher percentage of surviving patients, better progression free survival, and overall survival estimate after AA treatment. Of the eight variables analyzed, effectiveness in deferred CAB showed positive association to progression free survival (HR 0.29, 95% CI 0.12-0.67, p = 0.004) and overall survival (HR 0.24, 95% CI 0.07-0.81, p = 0.022). First line androgen deprivation therapy (ADT) duration also showed positive association to overall survival (HR 0.95, 95% CI 0.91-0.99, p = 0.023). Conclusions: Effectiveness of deferred CAB therapy was positively associated with progression free survival and overall survival of AA treatment after docetaxel. It can be used as a pre-treatment predictor.

20.
J Endourol Case Rep ; 3(1): 149-151, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29098199

RESUMO

Ectopic thyroid tissue in the adrenal gland (ETTAG) usually presents as a well-circumscribed cystic mass on a CT scan. However, the MRI features of ETTAG are incompletely understood. We report a case of ectopic thyroid tissue in the adrenal gland, which demonstrates findings similar to those of a pheochromocytoma on the MRI.

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