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1.
Ecancermedicalscience ; 11: 767, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28955403

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities. MATERIALS AND METHODS: This is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy. Paraffin-embedded tumour samples were reviewed by a single pathologist and tested for immunohistochemistry (IHC) expression of Ki-67, ERCC1, Bcl-2, and Lin28a. All images were evaluated by the same radiologist and RR was determined by RECIST 1.1. RESULTS: From July, 2006 to July, 2014, 142 patients were identified, being 82 (57.7%) SCLC and 60 (42.3%) EPNEC. Clinical characteristics and median Ki-67 (SCLC: 60%; EPNEC: 50%; p = 0.86) were similar between the groups. RR was higher for SCLC patients (86.8% versus 44.6%; p<0.001), but median OS was similar (10.3 months in SCLC and 11.1 months in EPNEC; HR 0.69, p = 0.07). Bcl-2 expression was higher in SCLC patients (46.3% versus 28.3%, p = 0.03) and was associated with worse prognosis in EPNEC (median OS 8.0 months versus 14.7 months; HR 0.47, p = 0.02). CONCLUSION: EPNEC patients presented inferior RR to platinum-based chemotherapy than SCLC but tended to live longer. Neither ERCC1, Lin28, or Ki-67 were prognostic or predictive for RR in EPNEC or SCLC. High Bcl-2 expression was associated with poor prognosis in EPNEC patients.

2.
Arq Bras Cir Dig ; 29(1): 9-13, 2016 Mar.
Artigo em Inglês, Português | MEDLINE | ID: mdl-27120731

RESUMO

BACKGROUND: Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients. AIM: In the second module of this consensus, management of resectable liver metastases was discussed. METHOD: Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities. RESULTS: Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions. CONCLUSION: Were presented validated ressectional strategies, to be taken into account in clinical practice.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Brasil , Terapia Combinada , Humanos
3.
ABCD arq. bras. cir. dig ; 29(1): 9-13, Jan.-Mar. 2016.
Artigo em Inglês | LILACS-Express | ID: lil-780014

RESUMO

Background : Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients. Aim : In the second module of this consensus, management of resectable liver metastases was discussed. Method : Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities. Results : Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions. Conclusion : Were presented validated ressectional strategies, to be taken into account in clinical practice.


Racional: As metástases hepáticas de câncer colorretal são evento frequente e potencialmente fatal na evolução dos pacientes. Objetivo : No segundo módulo desse consenso, foi discutido o manejo de metástases hepáticas ressecáveis. Método : Foi definido o conceito de metástases síncrônicas e metacrônicas, e ambos os cenários foram discutidos separadamente de acordo com as suas peculiaridades prognósticas e terapêuticas. Resultados : Foi dada especial atenção às missing metástases em resposta ao tratamento pré-operatório sistêmico, com ênfase em estratégias para evitar sua recorrência e como gerenciar as lesões desaparecidas. Conclusão : Foram apresentadas e validadas estratégias de ressecção em várias circunstâncias, para serem aplicadas na prática clínica.

4.
Ecancermedicalscience ; 10: 694, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28101137

RESUMO

OBJECTIVES: Spirituality is related to the care and the quality of life of cancer patients. Thus, it is very important to assess their needs. The objective of this study was the translation and cultural adjustment of the Spiritual Needs Assessment for Patients (SNAP) questionnaire to the Brazilian Portuguese language. METHODOLOGY: The translation and cultural adjustment of the SNAP questionnaire involved six stages: backtranslation, revision of backtranslation, translation to the original language and adjustments, pre-test on ten patients, and test and retest with 30 patients after three weeks. Adult patients, with a solid tumour and literate with a minimum of four years schooling were included. For analysis and consistency we used the calculation of the Cronbach alpha coefficient and the Pearson linear correlation. RESULTS: The final questionnaire had some language and content adjustments compared to the original version in English. The correlation analysis of each item with the total score of the questionnaire showed coefficients above 0.99. The calculation of the Cronbach alpha coefficient was 0.9. The calculation of the Pearson linear correlation with the test and retest of the questionnaire was equal to 0.95. CONCLUSION: The SNAP questionnaire translated into Brazilian Portuguese is adequately reliable and consistent. This instrument allows adequate access to spiritual needs and can help patient care.

5.
Ecancermedicalscience ; 9: 563, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26316884

RESUMO

BACKGROUND: In patients with adenocarcinoma of the pancreas, there are no standard second-line regimens. Many pre-clinical studies have shown that metformin alone or when combined with paclitaxel has antitumour effects on this tumour. We have tested here the combination of paclitaxel and metformin for patients with gemcitabine-refractory pancreatic cancer. METHODS: An uncontrolled phase II trial was carried out based on a two-stage Simon's design, with metformin and paclitaxel for patients with locally advanced or metastatic pancreatic cancer whose disease had progressed during first line treatment with a gemcitabine-based regimen. The primary endpoint was the disease control rate at eight weeks as per response evaluation criteria in solid tumours (RECIST) 1.1. Patients received paclitaxel 80 mg/m(2) weekly for three weeks every 28 days and metformin 850 mg p.o. t.i.d. continuously until progression or intolerance state was reached. RESULTS: Twenty patients were enrolled from July 2011 to January 2014: N = 6 (31.6%) achieved the primary endpoint, with all presenting stable disease. Median overall survival (OS) was 128 days (range 17-697) and the median progression free survival (PFS) was 44 days (range 14-210). Eight patients (40%) presented treatment-related G3-4 toxicities with the most common one being diarrhoea. CONCLUSIONS: Despite the encouraging pre-clinical evidence of the antitumour activity of metformin in adenocarcinoma of the pancreas, the primary endpoint of the disease control rate was not met. Besides, the treatment combination was poorly tolerated and could not be studied further. This study highlights the importance of performing clinical trials to reassure preclinical or observational data.

6.
Mol Clin Oncol ; 3(4): 793-796, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26171182

RESUMO

Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.

7.
Lancet Oncol ; 16(7): 859-70, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26095784

RESUMO

BACKGROUND: VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. METHODS: In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. FINDINGS: Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. INTERPRETATION: Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable. FUNDING: Eli Lilly and Co.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalos de Confiança , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Seleção de Pacientes , Modelos de Riscos Proporcionais , Indução de Remissão , Sorafenibe , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
8.
Med Oncol ; 31(11): 264, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25273866

RESUMO

Sorafenib is the first systemic therapy to demonstrate survival benefit in advanced hepatocellular carcinoma (HCC) in randomized controlled trials with rigorous patient selection. Neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with poor survival in various solid tumors. Our aim is to evaluate the prognostic role of NLR in HCC patients treated with sorafenib. A total of 105 advanced HCC patients treated with sorafenib were retrospectively reviewed, and relevant data from the clinical records were collected. Univariate and multivariate analysis were carried out to identify factors associated with survival. The median age of the cohort was 59.7 years, and 84.8 % were Child-Pugh class A, and 86.7 % had ECOG performance status 0 or 1. Median duration of sorafenib treatment was 100 days. Median overall survival (OS) of the entire cohort was 8.03 months. Median OS was 5.23 months (95 % CI 2.96-7.50 months) and 10.05 months (95 % IC 2.52-18.47 months) for patients with NLR > 3.5 and NLR ≤ 3.5, respectively (p = 0.002). Alpha-fetoprotein >1,030 ng/mL and serum albumin ≤3.8 g/dL were also associated with worse prognosis (p = 0.006 and p = 0.042, respectively). The subgroup of patients with high alpha-fetoprotein, low albumin and NLR > 3.5 had median OS of 1.7 months, whereas the subgroup with none of these parameters had median OS of 16.5 months (p < 0.001). NLR affects survival in advanced HCC patients treated with sorafenib. Selecting HCC patients based on the laboratorial features may improve the therapeutic effectiveness of sorafenib.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Linfócitos/metabolismo , Neutrófilos/metabolismo , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/farmacologia , Estudos Retrospectivos , Sorafenibe , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto Jovem
9.
Rev. Assoc. Med. Bras. (1992) ; 48(4): 297-302, out.-dez. 2002. tab
Artigo em Português | LILACS | ID: lil-330492

RESUMO

OBJETIVO: Avaliar os fatores preditivos de tratamento operatório nos doentes com úlceras pépticas hemorrágicas. MÉTODOS: Através de um estudo retrospectivo, foram analisados os prontuários dos doentes com úlceras pépticas hemorrágicas admitidos de 1998 a 2001. Foram avaliados 200 doentes, com idade entre 17 e 97 anos e média etária de 52 + 18 anos, sendo 153 (76,5 por cento) do sexo masculino. Dados vitais à admissäo, antecedentes mórbidos, achados e tratamento endoscópico, bem como a evoluçäo e tratamento definitivo foram revisados. Empregou-se o teste t de student e qui-quadrado para a análise estatística, considerando-se o valor de p< 0,05 como significativo. RESULTADOS: Vinte e sete (13,5 por cento) doentes foram admitidos em choque. A endoscopia da admissäo, 101 úlceras localizavam-se no duodeno e 99 no estômago, sendo classificadas como Forrest Ia em cinco (2,5 por cento), Ib em 20 (10 por cento), IIa em 48 (24 por cento) e IIb em 48 (24 por cento). Vinte e cinco doentes (12,5 por cento) foram operados, 23 (92 por cento) sendo submetidos à gastrectomia parcial com reconstruçäo a Billroth II. Os fatores associados à necessidade de tratamento operatório foram os antecedentes de alcoolismo (p=0,002), tabagismo (p=0,02), diabetes mellitus (p=0,01) e doença péptica (p=0,05), além de choque à admissäo (p<0,001) e lesöes Forrest Ia à endoscopia. Os doentes com lesöes Forrest IIb que näo receberam tratamento endoscópico à admissäo necessitaram tratamento cirúrgico com maior freqüência (p=0,012). CONCLUSÄO: Alcoolismo, tabagismo, antecedentes de doença péptica ou diabetes mellitus, instabilidade hemodinâmica à admissäo e lesöes Forrest Ia säo fatores preditivos de tratamento operatório nos doentes com úlceras pépticas hemorrágicas


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal , Úlcera Péptica Hemorrágica , Valor Preditivo dos Testes , Estudos Retrospectivos , Úlcera Gástrica , Resultado do Tratamento
10.
Rev Assoc Med Bras (1992) ; 48(4): 297-302, 2002 Oct-Dec.
Artigo em Português | MEDLINE | ID: mdl-12563456

RESUMO

OBJECTIVE: To analyze the predictors of operative treatment in patients sustaining bleeding peptic ulcers. METHODS: Retrospective analysis of the patients admitted owing to bleeding peptic ulcers from 1998 to 2001. Vital signs upon admission, associated diseases, endoscopy data, evolution and definitive care were evaluated. Patients who underwent surgery were compared with the others in order to identify the predictors of the operative treatment. Student's t and chi squared test were employed for statistical analysis, considering p< 0,05 as significant. RESULTS: Two hundred patients were included in the study group. The age ranged between 17 and 97 years (mean 52 + 18), and 153 patients (76.5%) were male. Shock upon admission was present in 27 (13.5%). The endoscopic exam performed at admission showed that 101 patients sustained ulcers in the duodenum and 99 in the stomach, which were classified as Forrest Ia in 5 (2.5%), Ib in 20 (10%), IIa in 48 (24%) and IIb in 48 (24%). Twenty five (12.5%) patients needed operation, and 23 (92%) were submitted to gastrectomy with Billroth's II reconstruction. The operative treatment were more frequently performed in patients sustaining chronic alcoholic intake (p=0.002), cigarette smoking (p=0.02), diabetes mellitus (p=0.01), chronic peptic disease (p=0.05), shock upon admission (p<0.001) and spurting activity at the endoscopy (p<0.001). Forrest IIb lesions which did not receive any form of endoscopic treatment at admission were more likely to rebleed (p=0.012). CONCLUSIONS: The predictors of operative treatment were chronic alcoholic intake, smoke addiction, diabetes mellitus, chronic peptic disease, shock upon admission and Forrest Ia ulcers.


Assuntos
Úlcera Péptica Hemorrágica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/etiologia , Úlcera Péptica Hemorrágica/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Úlcera Gástrica/complicações , Úlcera Gástrica/patologia , Resultado do Tratamento
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