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The diagnosis of breast cancer in early stage is essential for successful treatment. Detection can be performed in several ways, the most common being through mammograms. The projections acquired by this type of examination are directly affected by the composition of the breast, which density can be similar to the suspicious masses, being a challenge the identification of malignant lesions. In this article, we propose a computer-aided detection (CAD) system to aid in the diagnosis of masses in digitized mammograms using a model based in the U-Net, allowing specialists to monitor the lesion over time. Unlike most of the studies, we propose the use of an entire base of digitized mammograms using normal, benign, and malignant cases. Our research is divided into four stages: (1) pre-processing, with the removal of irrelevant information, enhancement of the contrast of 7989 images of the Digital Database for Screening Mammography (DDSM), and obtaining regions of interest. (2) Data augmentation, with horizontal mirroring, zooming, and resizing of images; (3) training, with tests of six-based U-Net models, with different characteristics; (4) testing, evaluating four metrics, accuracy, sensitivity, specificity, and Dice Index. The tested models obtained different results regarding the assessed parameters. The best model achieved a sensitivity of 92.32%, specificity of 80.47%, accuracy of 85.95% Dice Index of 79.39%, and AUC of 86.40%. Even using a full base without case selection bias, the results obtained demonstrate that the use of a complete database can provide knowledge to the CAD expert.
Assuntos
Neoplasias da Mama , Aprendizado Profundo , Neoplasias da Mama/diagnóstico por imagem , Diagnóstico por Computador , Detecção Precoce de Câncer , Feminino , Humanos , Mamografia , Redes Neurais de ComputaçãoRESUMO
Estrogen has been shown to play an important role in pituitary tumor pathogenesis. In humans, this biosynthesis is mediated by aromatase, an enzyme that converts androgens to estrogens. Just a few studies about aromatase expression in human pituitary gland, both in normal and pathological ones, are found in the literature. This study aimed to assess aromatase enzyme expression in human pituitary adenomas and associate it with gender, tumor size and tumor subtype. We conducted a cross-sectional study, reviewed clinical data and surgical specimens of consecutive 65 patients (35 women and 30 men) with anatomopathologic diagnosis of pituitary adenoma who underwent adenomectomy at a neurosurgical referral center in southern Brazil. Immunohistochemistry was performed to assess aromatase expression and define tumor subtype, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to estimate aromatase gene expression. Mean patient age was 45.6 (±13.3) years (range, 18 to 73 years), 86.2% of our samples were macroadenomas while 13.8% were classified as microadenomas. Based on clinical and immunohistochemical data, 23 (35.4%) patients had non-functioning adenomas, 19 (29.2%) had somatotroph adenomas (acromegaly), 12 (18.5%) had lactotroph adenomas (hyperprolactinemic syndrome), and 11 (16.9%) had corticotroph adenomas (Cushing's disease). Immunohistochemical analysis was performed in 59 cases, and 58 (98.3%) showed no aromatase expression. Quantification by qRT-PCR was performed in 43 samples, and 36 (83.7%) revealed no gene expression. Among tumor specimens examined by both techniques (37 cases), 30 showed no gene or protein expression (concordance index, 0.81). It is possible to mention that aromatase expression was lost in most pituitary adenomas, regardless of gender, tumor subtype, or tumor size.
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Adenoma/enzimologia , Aromatase/metabolismo , Neoplasias Hipofisárias/enzimologia , Adenoma/classificação , Adenoma/patologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipersecreção Hipofisária de ACTH/enzimologia , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Wilms tumor (WT) is the most common renal malignancy of childhood. The aim of this study was to verify the epidemiological profile and prognosis of a sample of patients from Brazil and compare them to similar data from other Latin American studies. METHOD: The sample consisted of consecutive patients diagnosed with WT in an oncohematology service of a referral hospital in Southern Brazil, between 1989 and 2009. Clinical, radiological, pathological and survival data were collected from the medical records. Analysis was done using Excel and SPSS version 18.0. The significance level was set at P < 0.05. RESULTS: The final sample consisted of 45 patients. The male/female ratio was 1.25:1. Mean age at diagnosis was 43.9 months and all patients were of European descent. Thirty-three patients (73.3%) had both signs/symptoms of abdominal mass and hypertension. Malformation was observed in nine patients (20%) and there was one case of Fanconi's anemia (2.2%). Three patients had bilateral disease (6.7%). The majority of patients had stage III and IV (62.2%). Patients with malformation had an earlier age at diagnosis (P = 0.018) and a higher prevalence of bilateral disease (P = 0.044). Overall survival was 75%. Age at diagnosis was the only significant independent predictor associated with death. CONCLUSION: Death is closely related to late diagnosis in WT. Oncologic services should also be concerned about morbidity caused by therapeutic options in cases of late diagnosis, and the consequences for quality of life.
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Neoplasias Renais/epidemiologia , Tumor de Wilms/epidemiologia , Brasil/epidemiologia , Pré-Escolar , Feminino , Hospitais , Humanos , Lactente , América Latina , Masculino , PrognósticoRESUMO
INTRODUCTION: Gastric epithelial tumors exhibit morphological heterogeneity, diverse biological behaviors, and different oncopathological pathways. The Cancer Genome Atlas (TCGA) proposed a molecular classification of gastric adenocarcinomas based on genetic and molecular findings, which shows particular characteristics of diagnosis, prognosis, and indirectly, therapeutic alternatives. Within this classification, Epstein-Barr virus-positive (EBV+) and high microsatellite instability (MSI-H) subtypes stand out as subtypes that present a less aggressive biological behavior and a highly mutilated phenotype. This study conducted a systematic review with an emphasis on epidemiological and prognostic factors based on the molecular classification proposed by TCGA. METHODS: A broad, comprehensive, and reproducible search with methodological rigor was conducted for study selection using the ROBINS-I and GRADEpro protocols and appropriate combinations of keywords. RESULTS: A total of 25 studies were selected: six with a complete classification similar to TCGA and 19 with a distinction between MSI-H and EBV+. The application of meta-analysis calculations reinforces the prevalence of positive Epstein-Barr adenocarcinomas in males and high microsatellite instability in females, with a high level of certainty of evidence and low risk of bias in the analyzed studies due to the rigorous methods used. CONCLUSION: The molecular classification proposed by TCGA shows limited dissemination, with MSI-H and EBV+ subtypes being the most researched, probably due to the benefit of the association with immunotherapies. However, the subclassification cannot be restricted to less than a quarter of the cases, and improvements in this aspect are urgent for the construction of knowledge on this important topic of global health.
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Adenocarcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Masculino , Feminino , Humanos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/complicações , Instabilidade de Microssatélites , Repetições de Microssatélites , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma/patologiaRESUMO
BACKGROUND: In cutaneous melanomas in general, tumor inflammatory infiltrate (TII) can protect against distant metastases, but there is no consensus when only thin primary cutaneous melanomas (TPCM) are considered. OBJECTIVE: To investigate the presence of TII in TPCM and the relationship between TII and the occurrence of metastases. METHODS: Case-control study including 50 patients with TPCM, 22 metastatic (MC group) and 28 non-metastatic (NMC group). The presence of TII was evaluated and, if present, qualified as mild, moderate or marked. RESULTS: The mean age was 50.7 years in the MC and 56.2 years in the NMC group (pâ¯=â¯0.234), and the male sex predominated in the MC group (63.6%). The average Breslow thickness was higher in the MC when compared to that observed in the NMC (respectively 0.8 vs. 0.6â¯mm, pâ¯=â¯0.012). The presence of ulceration occurred in 22.7% of the MC and 17.9% of the NMC (pâ¯=â¯0.732). TII was present in all 50 TPCM, being marked or moderate in 67.9% of the NMC and 54.5% in the MC group (pâ¯=â¯0.503). In the multivariate analysis, the presence of moderate and marked TII had an Odds Ratio (OR) of 0.57 (95% Confidence Interval [CI]: 0.18â1.8) and adjusted OR of 0.68 (95% CI 0.13â3.99). STUDY LIMITATIONS: Small sample size. CONCLUSIONS: TII was present in all TPCM (with and without metastases), and it was not possible to demonstrate a protective effect of TII against the appearance of metastases.
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Melanoma , Neoplasias Cutâneas , Humanos , Masculino , Pessoa de Meia-Idade , Melanoma/patologia , Neoplasias Cutâneas/patologia , Estudos de Casos e Controles , Prognóstico , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Breast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis. METHODS: We will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer. A sensitive search strategy will be employed in MEDLINE, EMBASE, LILACS, The Grey Literature Report, OpenGrey, OAIster, and Cochrane CENTRAL. Two reviewers will independently screen all identified references for eligibility and extract data. The outcomes evaluated will be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive Lymph Node, and Distant Metastasis. The outcomes will be extracted directly from the studies, if available. Methodological quality and bias of included studies will be assessed using a standardized checklist and overall quality of evidence will be assessed through the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. If meta-analysis is possible, the measures of association will be calculated using bivariate random-effects models. Statistical heterogeneity will be evaluated with I2 statistics and explored through sensitivity analysis. DISCUSSION: Immunomodulation seems to be a promising strategy in solid tumors. Breast cancer is the most common malignancies in women worldwide, and one of the leading causes of cancer death. PD-1 and PD-L1 are key physiologic suppressors of the cytotoxic immune reaction. TRIAL REGISTRATION: Systematic review registration: CRD42019121118 (PROSPERO).
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Antineoplásicos , Neoplasias da Mama , Antígeno B7-H1 , Testes Diagnósticos de Rotina , Feminino , Humanos , Metanálise como Assunto , Prognóstico , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins' combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepartum diagnosis is important to the management, preoperative planning, and outcomes. Prenatal imaging exams like echocardiography, CT, MRI, and ultrasonography are feasible and can provide relevant information about malformation severity and prognosis.
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Gravidez de Gêmeos , Gêmeos Unidos , Feminino , Humanos , Gravidez , Diagnóstico Pré-Natal , Gêmeos , Ultrassonografia Pré-Natal , Adulto JovemRESUMO
PURPOSE: Enhancer of zeste homolog 2 (EZH2) is associated with epigenetic gene silencing and aggressiveness in many tumor types. However, the prognostic impact of high EZH2 expression is controversially discussed for colorectal cancer. For this reason, we immunohistochemically analyzed EZH2 expression in 105 specimens from colon cancer patients separately for tumor center and invasion front. METHODS: All sections from tissue microarrays were evaluated manually and digitally using Definiens Tissue Studio software (TSS). To mirror-image the EZH2 status at the tumor invasion front, we treated HCT116 colon cancer cells with the EZH2 inhibitor 3-Deazaneplanocin A (DZNep) and studied the growth of in ovo xenografts in the chorioallantoic membrane (CAM) assay. RESULTS: We showed a significant decrease in EZH2 expression and the repressive H3K27me3 code at the tumor invasion front as supported by the TSS-constructed heatmaps. Loss of EZH2 at tumor invasion front, but not in tumor center was correlated with unfavorable prognosis and more advanced tumor stages. The observed cell cycle arrest in vitro and in vivo was associated with higher tumor aggressiveness. Xenografts formed by DZNep-treated HCT116 cells showed loosely packed tumor masses, infiltrative growth into the CAM, and high vessel density. CONCLUSION: The differences in EZH2 expression between tumor center and invasion front as well as different scoring and cutoff values can most likely explain controversial literature data concerning the prognostic value of EZH2. Epigenetic therapies using EZH2 inhibitors have to be carefully evaluated for each specific tumor type, since alterations in cell differentiation might lead to unfavorable results.
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Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Margens de Excisão , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/metabolismo , Embrião de Galinha , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Regulação para Baixo , Feminino , Células HCT116 , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Análise Serial de TecidosRESUMO
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5-fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
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Benzoquinonas/farmacologia , Neoplasias Colorretais/genética , Citotoxinas/farmacologia , Fluoruracila/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Antígeno AC133/metabolismo , Animais , Benzoquinonas/química , Adesão Celular/efeitos dos fármacos , Embrião de Galinha , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Citotoxinas/química , Fluoruracila/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Organoides/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5%), >20% of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40%) and 8 (20%) cases, respectively. P53 was positive in 18 (45%) cases, with 11 (61%) weakly positive and 7 (39%) strongly positive. HER2 was positive in 23 (57.5%) of the samples and did not show statistical association with survival (p=0.07).
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Biomarcadores Tumorais/metabolismo , Neoplasias Cerebelares/patologia , Meduloblastoma/patologia , Adolescente , Antígenos Nucleares/metabolismo , Brasil/epidemiologia , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/mortalidade , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Humanos , Lactente , Antígeno Ki-67/metabolismo , Masculino , Meduloblastoma/metabolismo , Meduloblastoma/mortalidade , Neoplasia Residual , Proteínas do Tecido Nervoso/metabolismo , Receptor ErbB-2/metabolismo , Sinaptofisina/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Abstract Background In cutaneous melanomas in general, tumor inflammatory infiltrate (TII) can protect against distant metastases, but there is no consensus when only thin primary cutaneous melanomas (TPCM) are considered. Objective To investigate the presence of TII in TPCM and the relationship between TII and the occurrence of metastases. Methods Case-control study including 50 patients with TPCM, 22 metastatic (MC group) and 28 non-metastatic (NMC group). The presence of TII was evaluated and, if present, qualified as mild, moderate or marked. Results The mean age was 50.7 years in the MC and 56.2 years in the NMC group (p = 0.234), and the male sex predominated in the MC group (63.6%). The average Breslow thickness was higher in the MC when compared to that observed in the NMC (respectively 0.8 vs. 0.6 mm, p = 0.012). The presence of ulceration occurred in 22.7% of the MC and 17.9% of the NMC (p = 0.732). TII was present in all 50 TPCM, being marked or moderate in 67.9% of the NMC and 54.5% in the MC group (p = 0.503). In the multivariate analysis, the presence of moderate and marked TII had an Odds Ratio (OR) of 0.57 (95% Confidence Interval [CI]: 0.18‒1.8) and adjusted OR of 0.68 (95% CI 0.13‒3.99). Study limitations Small sample size. Conclusions TII was present in all TPCM (with and without metastases), and it was not possible to demonstrate a protective effect of TII against the appearance of metastases.
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Introduction: Breast cancer is a complex and heterogeneous disease which is increasingly important as a public health problem. In Brazil, 57,960 new cases have been estimated to be the burden in 2016 and 2017. Despite advances in early diagnosis and therapy, approximately 20-30% of patients, even with early stage lesions, will develop distant metastatic disease. Tumors with similar clinical and pathological presentations may have differing behavior, so it is important to understand specific biological characteristics. Objective: To investigate tumor markers of primary tumors featuring pleural metastasis to identify organ-specific characteristics of metastatic breast cancer. Methods: In a historical cohort study, immunohistochemistry was performed on cell blocks of neoplastic pleural effusions and results were compared with clinicopathological data. Results: The median survival time with Her-2 overexpression in malignant pleural effusions was 2.2 months, whereas cases without overexpression survived, on average, for seven months (p = 0.02). Conclusions: We emphasize that metastases may behave independently of primary tumors, but the present results indicate that therapeutic agents targeting Her-2 overexpression could increase survival in metastatic breast cancer cases.
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SUMMARY BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins' combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepartum diagnosis is important to the management, preoperative planning, and outcomes. Prenatal imaging exams like echocardiography, CT, MRI, and ultrasonography are feasible and can provide relevant information about malformation severity and prognosis.
RESUMO BACKGROUND: Gêmeos parasitas assimétricos ou heterópagos são uma ocorrência rara, com incidência de um caso em 1-2 milhões. Os gêmeos siameses são classificados de acordo com sua simetria, local de fusão e grau de duplicação. MÉTODOS: Relatamos aqui uma apresentação extremamente rara de gêmeos parasitários não descritos anteriormente. São descritas alterações macro e microscópicas e discutidos aspectos relevantes dessa malformação e da importância do diagnóstico pré-natal. RESULTADOS: Um caso de uma paciente de 23 anos de idade, com gestação monocoriônica, monoamniótica de gêmeos siameses assimétricos diagnosticada com 29 semanas de idade gestacional. Acreditamos que este relato chama a atenção para esta apresentação e para a importância do cuidado e manejo pré-natal. Os fetos nasceram de parto vaginal já sem vida, pesando em conjunto 1.300 gramas, e eram unidos pela região cervical esquerda. CONCLUSÃO: Este relato pode ajudar a encontrar estratégias para a decisão clínica em casos futuros. O diagnóstico pré-natal é fundamental para o manejo e planejamento pré-operatório. Exames de imagem como ecocardiografia, tomografia computadorizada, ressonância magnética e ultrassonografia são factíveis e podem fornecer informações-chave sobre a gravidade e prognóstico da malformação.
Assuntos
Humanos , Feminino , Gravidez , Adulto Jovem , Gêmeos Unidos , Gravidez de Gêmeos , Diagnóstico Pré-Natal , Gêmeos , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ >500 mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10 mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable.
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Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Tumor de Wilms/mortalidade , Tumor de Wilms/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Neoplasias Renais/terapia , Masculino , Prognóstico , Taxa de Sobrevida , Carga Tumoral , Tumor de Wilms/terapiaRESUMO
PURPOSE: Small cell lung cancer (SCLC) is a highly aggressive tumor, and few studies have examined the amplification status of the MYC gene in tumor samples using chromogenic in situ hybridization (CISH). Emerging target treatments associated with MYC status in SCLC necessitates the evaluation of MYC using current methodologies, such as CISH. In this study, we evaluated tissue samples from untreated patients to determine the relation between MYC amplification and clinical and pathological factors, including survival. METHODS: Formalin-fixed paraffin-embedded tumor samples were obtained from 77 patients with SCLC who underwent a diagnostic biopsy for SCLC. The samples were analyzed by CISH using a MYC probe (ZytoDot(®) CISH probe). The relationship between cytogenetic analysis, pathologic characteristics and survival time was evaluated using the Chi-square test, Fisher's test and Mann-Whitney method. A regression model was constructed to exclude any confounding factors. RESULTS: Of 77 samples, 64.9 % were from bronchi biopsy and the remainder was from the mediastinal, cervical and supraclavicular lymph nodes. The MYC oncogene was amplified in 20 % of the tumors. After the multivariate regression analysis, patients with MYC amplification had a significantly shorter survival time (4.67 weeks) versus patients without MYC amplification (26.15 weeks) (p = 0.02, CI 1.355-10.261). CONCLUSION: MYC amplification is a frequent event in SCLC and is related to a short survival time. MYC amplification may be an independent prognostic factor for SCLC. Further studies are required to support this finding and clarify the role of MYC in SCLC tumorigenesis.
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Amplificação de Genes , Genes myc , Hibridização In Situ , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .
OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .
Assuntos
Animais , Humanos , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Compostos Macrocíclicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Euphorbia/química , Compostos Macrocíclicos/química , Compostos Macrocíclicos/isolamento & purificação , Conformação Molecular , Fenótipo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Medulloblastoma (MB) is the most common malignant brain tumor in childhood. The alterations found include: presence of oncoproteins p53 and HER2, elevated mitotic index, and presence of neuronal differentiation. The aim of this study was to determine the immunohistochemical expression of markers Ki-67, NeuN, synaptophysin, HER2 and p53 in 40 MB samples and their correlation with clinicopathologic parameters and survival. In 29 patients (72.5 percent), >20 percent of cells were positive for Ki-67. Males showed greater ki-67 expression (p=0.02) and smaller survival rates (p=0.002). NeuN and synaptophysin were negative in 16 (40 percent) and 8 (20 percent) cases, respectively. P53 was positive in 18 (45 percent) cases, with 11 (61 percent) weakly positive and 7 (39 percent) strongly positive. HER2 was positive in 23 (57.5 percent) of the samples and did not show statistical association with survival (p=0.07).
Meduloblastoma (MB) é o tumor maligno encefálico mais freqüente na infância. dentre as alterações encontradas estão: a presença das oncoproteínas p53 e HER2, elevado índice mitótico e presença de diferenciação neuronal. o objetivo deste estudo foi determinar a expressão imunoistoquímica (IMQ) dos marcadores Ki-67, NeuN, sinaptofisina, HER2 e p53 em 40 amostras de MB, correlacionando-as com parâmetros clinicopatológicos e com a sobrevida. Vinte e nove pacientes (72,5 por cento) apresentaram 20 por cento ou mais das células positivas para Ki-67. os pacientes do sexo masculino apresentaram maior expressão do Ki-67 (p=0,02) e também menor sobrevida (p=0,002). NeuN e sinaptofisina foram negativos em 16 (40 por cento) e 8 (20 por cento) casos, respectivamente. P53 foi positivo em 18 (45 por cento) casos, sendo 11 (61 por cento) fracamente positivos e 7 (39 por cento) fortemente positivos. HER2 foi positivo em 23 (57,5 por cento) das amostras e não demonstrou associação estatística com a sobrevida (p=0.07).