Assuntos
Ensaios Enzimáticos Clínicos , Técnicas de Apoio para a Decisão , Resistência à Insulina , Cirrose Hepática/diagnóstico , Testes de Função Hepática , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Glicemia/análise , Diagnóstico Diferencial , Humanos , Insulina/sangue , Queratina-18/sangue , Cirrose Hepática/sangue , Cirrose Hepática/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Gastric cancer is the 3rd most common cause of death in men and the 5th common in women worldwide. Today, surgery is the only curative therapy. Currently available advanced imaging modalities can predict R0 resection in most patients, but it can only be detected with certainty in the perioperative period. AIM: To determine the role of serum CK18, MMP9, TIMP1 levels in predicting R0 resection in patients with gastric cancer. METHODS: Fifty consecutive patients scheduled for curative surgery with gastric adenocarcinoma diagnosed between 2013-2015 were included. One ml of blood was taken from the patients to analyze CK18, MMP9 and TIMP1. RESULTS: CK18, MMP9 and TIMP1 levels were positively correlated with pathological N and the stage (p<0,05). CK-18, MMP-9 and TIMP-1 averages in positive clinical lymph nodes and in clinical stage 3, were found to be higher than the averages of those with negative clinical lymph nodes and in clinical stage 2 (p<0,05). CONCLUSION: Although serum CK-18, MMP-9 and TIMP-1 preoperatively measured in patients scheduled for curative surgery did not help to evaluate gastric tumor resectability, they were usefull in predicting N3-stage.
Assuntos
Adenocarcinoma/sangue , Adenocarcinoma/cirurgia , Queratina-18/sangue , Metaloproteinase 9 da Matriz/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/cirurgia , Inibidor Tecidual de Metaloproteinase-1/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Feminino , Humanos , Modelos Logísticos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valores de Referência , Estatísticas não Paramétricas , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has been increasing constantly and linked to the global obesity epidemic. The NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma. Liver biopsy is the only reliable means to diagnose and stage NASH, but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition and cell-death markers, which correlate with liver injury in an NAFLD patient cohort. PATIENTS AND METHODS: Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. Matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloproteinase inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)] were measured in serum samples. RESULTS: HA showed an association with fibrosis severity (P=0.03) and M30 with steatosis (P=0.013), inflammation (P=0.004), and fibrosis severity (P=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The evaluation of diagnostic accuracy showed good performance as less invasive markers of significant fibrosis of both HA (area under the receiver operating characteristic curve: 0.928) and M30 (area under the receiver operating characteristic curve: 0.848). CONCLUSION: Biomarkers are essential tools that may provide a quick and accurate diagnosis for patients with life-threatening NAFLD and NASH. HA and M30, together or determined sequentially, have been found to be straightforward tests that may be sufficient to predict significant fibrosis even in a primary care center of an underdeveloped country.
Assuntos
Ácido Hialurônico/sangue , Queratina-18/sangue , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Área Sob a Curva , Argentina , Biomarcadores/sangue , Biópsia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inibidor Tecidual de Metaloproteinase-1/sangueRESUMO
ABSTRACT Background: Gastric cancer is the 3rd most common cause of death in men and the 5th common in women worldwide. Today, surgery is the only curative therapy. Currently available advanced imaging modalities can predict R0 resection in most patients, but it can only be detected with certainty in the perioperative period. Aim: To determine the role of serum CK18, MMP9, TIMP1 levels in predicting R0 resection in patients with gastric cancer. Methods: Fifty consecutive patients scheduled for curative surgery with gastric adenocarcinoma diagnosed between 2013-2015 were included. One ml of blood was taken from the patients to analyze CK18, MMP9 and TIMP1. Results: CK18, MMP9 and TIMP1 levels were positively correlated with pathological N and the stage (p<0,05). CK-18, MMP-9 and TIMP-1 averages in positive clinical lymph nodes and in clinical stage 3, were found to be higher than the averages of those with negative clinical lymph nodes and in clinical stage 2 (p<0,05). Conclusion: Although serum CK-18, MMP-9 and TIMP-1 preoperatively measured in patients scheduled for curative surgery did not help to evaluate gastric tumor resectability, they were usefull in predicting N3-stage.
RESUMO Racional: Câncer gástrico é a terceira causa mais comum de morte em homens e a quinta em mulheres em todo o mundo. Atualmente a cirurgia é a única terapia curativa. As modalidades de imagem avançadas atualmente disponíveis podem prever a ressecção R0 na maioria dos pacientes, mas ela só pode ser detectada durante o perioperatório. Objetivo: Determinar o papel dos níveis séricos de CK18, MMP9 e TIMP1 na predição da ressecção R0 em pacientes com câncer gástrico. Métodos: Foram incluídos no estudo pacientes consecutivos agendados para operação curativa entre 2013-2015. Foi retirado 1 ml de sangue dos pacientes incluídos para estudar CK18, MMP9 e TIMP1. Resultados: Os níveis de CK18, MMP9 e TIMP1 foram positivamente correlacionados com o N patológico e o estadiamento (p<0,05). As médias CK-18, MMP-9 e TIMP-1 das pessoas com linfonodos positivos e aqueles em estágio clínico 3 foram superiores às médias das pessoas com linfonodos negativos e estágio clínico 2 (p<0,05). Conclusão: Embora as dosagens séricas de CK-18, MMP-9 e TIMP-1 em pacientes agendados para operação curativa por adenocarcinoma gástrico não ajudem a ter ideia de ressecabilidade tumoral, ela foi útil na predição de estadiamento N3.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/sangue , Adenocarcinoma/cirurgia , Adenocarcinoma/sangue , Metaloproteinase 9 da Matriz/sangue , Queratina-18/sangue , Valores de Referência , Neoplasias Gástricas/patologia , Adenocarcinoma/patologia , Biomarcadores Tumorais/sangue , Modelos Logísticos , Estatísticas não Paramétricas , Inibidor Tecidual de Metaloproteinase-1/sangue , Metástase Linfática/patologia , Estadiamento de NeoplasiasRESUMO
Nonalcoholic steatohepatitis (NASH) is the most aggressive form of nonalcoholic fatty liver disease (NAFLD) and involves the risk of progression to more advanced stages of liver disease. Non-invasive methods are needed to identify patients with NASH. OBJECTIVE: To evaluate the diagnostic performance of the determination of serum levels of cytokeratin-18 (CK-18) as a non-invasive marker of NASH in the Chilean population. METHODS: Serum CK-18 levels were determined in a group of 41 patients with biopsy-proven NAFLD. NASH diagnosis was based on Brunt's criteria (histological parameters and ballooning), and the NAFLD activity score (NAS) and the presence of fibrosis were determined. The correlation between the NAFLD activity score (NAS) and CK-18 was evaluated with Spearman's rank correlation coefficient. A ROC curve was produced to assess the diagnostic value of CK-18 for NASH. The NAFLD fibrosis score (NFS) (to predict fibrosis and NASH) was compared to CK-18 with simple linear regression. Data were expressed in median [25th-75th percentile] and evaluated with the Wilcoxon rank test. RESULTS: The mean age of the study group (23% male) was 50.4±11.1 years. 34.2% were diagnosed with NASH (NAS≥5). CK-18 levels were significantly higher in patients with NASH versus those without NASH (183.6 IU/l [97.4 to 734.4] vs. 117.2 IU/l [83.8 to 954.8], p= 0.016). CK-18 levels were a good predictor of NASH on biopsy with an area under the curve (AUC) of 0.732 (95% CI, 0.572 to 0.897). A CK-18 cut-off of 130.5 IU/l had a sensitivity of 92.9%, specificity of 63%, positive predictive value of 56.5% and negative predictive value of 94.4%, and was able to correctly classify 73.2% of patients with NASH. NFS identified advanced liver fibrosis (AUC 0.739, 95% CI, 0.56-0.91), but was of limited value to identify NASH (AUC 0.413, 95% CI, 0.21-0.61). CONCLUSION: CK-18 is a good non-invasive marker for NASH. Although NFS was found to be an accurate marker of advanced liver fibrosis, it was not of value to identify NASH. In patients with NAFLD, CK-18 and NFS could be useful in predicting NASH and liver fibrosis, respectively.
Assuntos
Queratina-18/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Biomarcadores/sangue , Biópsia , Chile/epidemiologia , Feminino , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Paclitaxel is an effective treatment for some of the non-small-cell lung cancer (NSCLC) patients. However, prediction of the outcome of paclitaxel treatment at the early stage of the chemotherapy is difficult. M30 and M65 are circulating fragments of cytokeratin 18 released during apoptosis or necrosis, respectively, and have been used as markers to evaluate chemotherapy in some cancers. Here, we aimed to examine M30 and M65 values for predicting the therapeutic outcome of paclitaxel treatment of NSCLC. METHODS: The serum levels of M30 and M65 before and after paclitaxel treatment in advance-stage NSCLC patients were analyzed, and compared to those in healthy controls. The importance of the M30 and M65 levels to the outcome of chemotherapy was analyzed. RESULT: We found that the serum M30 and M65 levels were higher in patients with NSCLC (n = 44) than in control healthy subjects (n = 56) (p < 0.001). Two days after paclitaxel treatment, the serum levels of both M30 and M65 significantly increased in NSCLC patients (p < 0.001). Neither marker alone significantly correlated with overall patient survival, but the ratio of M30 vs M65 appeared to be an important prognostic factor for the overall survival of the patients (p < 0.01). CONCLUSION: Our results suggest that the serum M30/M65 ratio may be a prognostic factor for the outcome of paclitaxel treatment in NSCLC.
Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Queratina-18/sangue , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is involved in the formation of intracellular cytoskeleton, and has been considered a promising apoptosis marker in gastrointestinal carcinomas. Growth factors, including hepatocyte growth factor (HGF), may provide a microenvironment for malignant cells. In this study, we aimed to compare serum HGF and CK18 levels between esophageal squamous cell carcinoma patients and healthy controls. The study included 41 adult patients (20 male, 21 female) diagnosed with esophageal squamous cell carcinoma, with a mean age of 63.54 ± 10.88 years (range, 41-82 years). We also recruited 39 age and gender-matched healthy control subjects. Venous blood samples were taken; serum HGF and CK18 concentrations were determined via ELISA. Results indicated that serum HGF levels were higher in patients (1.37 ± 0.63 ng/mL) as compared to the healthy subjects (0.41 ± 0.29 ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 ± 1.33 ng/mL) than in the control group (0.34 ± 0.23 ng/mL) (P < 0.001). In addition, serum HGF and CK18 levels were positively correlated with metastasis stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To our knowledge, this is the first study to evaluate serum HGF and CK18 levels in patients with esophageal squamous cell carcinoma. The results suggest that serum CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers of esophageal squamous cell carcinoma.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Fator de Crescimento de Hepatócito/genética , Queratina-18/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Feminino , Expressão Gênica , Fator de Crescimento de Hepatócito/sangue , Humanos , Queratina-18/sangue , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Microambiente Tumoral/genéticaRESUMO
Background. Chemerin and retinol binding protein-4 (RBP-4) are adipokines which may play a role in the progression of NAFLD. It has been also suggested that cytokeratin-18 (CK-18) could be a marker of hepatocyte caspase-directed death while transgelin-2 production could reflect stage of liver fibrosis. The aim of this study was to evaluate the level of the above adipokines in sera of patients with NAFLD and determine the relation between the level of transgelin-2 and fibrosis-4 index (FIB-4). MATERIAL AND METHODS: Ninety-five subjects included initially to the study were divided into four groups: (I) prediabetics, obese with NAFLD and metabolic syndrome (MS), (II) lean with NAFLD and without MS, (III) obese without NAFLD and MS, and (IV) healthy individuals. We determined the levels of chemerin, RBP-4, transgelin-2 and CK-18 fragments in sera of patients with NAFLD. Moreover, we examined if the levels of CK-18 fragments and transgelin-2 correlates with FIB4 value. RESULTS: Chemerin and RBP-4 were highly expressed in sera of all NAFLD, especially in obese individuals. Chemerin level was also linked to MS. High level of serum CK-18 fragments and transgelin-2 did not correlate with obesity and MS, but seemed to correlate with progression of NAFLD to liver fibrosis. CONCLUSIONS: In conclusion, the production of the two adipokines, chemerin and RBP-4, is strongly associated with obesity in patients with NAFLD. Serum concentrations of CK-18 fragments and transgelin-2 correlate with the severity of NAFLD, but no with obesity.
Assuntos
Quimiocinas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Queratina-18/sangue , Proteínas dos Microfilamentos/sangue , Proteínas Musculares/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Proteínas Plasmáticas de Ligação ao Retinol/análise , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/sangue , Obesidade/diagnóstico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Diagnosis of non-alcoholic fatty liver disease (NAFLD) is limited by the need for liver biopsies. Serum cytokeratin 18 (CK-18) levels have been investigated as potential biomarkers for the presence of NAFLD and non-alcoholic steatohepatitis (NASH). Herein, we assessed the correlation between CK-18 levels and NAFLD progression. MATERIAL AND METHODS: Serum CK-18 levels were estimated using the M30 antibody enzyme-linked immunosorbent assay in 147 patients diagnosed with NAFLD. In 72 patients, disease progression was evaluated by repeated liver biopsy, which was conducted after 4.3 ± 2.6 years. The relationship between the CK-18 levels and liver histological findings was assessed. RESULTS: The CK-18 levels were useful for identifying NAFLD patients with NAFLD activity scores (NAS) ≥ 5 (NAS ≥ 5 vs. ≤ 4: 675.1 U/L vs. 348.7 U/L; p < 0.0001). A cut-off value of 375 U/L was calculated using the receiver operating characteristic curve approach, with a specificity and sensitivity of 81.5 and 65%, respectively, for the diagnosis of NASH. Among the 72 patients who underwent repeated liver biopsy, 11 patients with a progressed NAS also had significantly increased serum CK-18 levels (p < 0.01); in 30 patients with an improved NAS, there was a significant improvement in the mean CK-18 levels (p < 0.0001). The 31 patients with static NAS had static CK-18 levels. CONCLUSIONS: In conclusion, serum CK-18 levels can predict NAS ≥ 5 in NAFLD patients. In NAFLD patients, serum CK-18 levels reflect NAS values and correlate with histological changes, and they appear to be useful indicators of progression and improvement.
Assuntos
Queratina-18/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Biópsia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , Valor Preditivo dos Testes , Curva ROC , Indução de Remissão , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND AND RATIONALE: Insulin resistance (IR), adipocytokines, oxidative stress and hepatic apoptosis play a pathogenetic role in nonalcoholic fatty liver disease (NAFLD). AIMS: The evaluation of specific adipocytokines and markers of IR, oxidative stress and apoptosis in NAFLD patients; the introduction of a combined non-invasive index for nonalcoholic steatohepatitis (NASH). MATERIAL AND METHODS: Thirty patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 15 with NASH) and 24 controls were recruited. Blood samples for total and high molecular weight (HMW) adiponectin, visfatin and tumor necrosis factor (TNF)-α, the apoptotic by-product cytokeratin (CK)-18, the reactive oxygen metabolites (ROMs) and standard biochemical tests were measured. Homeostatic model of assessment - insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated. MAIN RESULTS: Total and HMW adiponectin were significantly lower and TNF-α higher in either NAFL or NASH group compared to control group; CK-18 was significantly higher in NASH compared to either NAFL or control group. CHAI (an acronym of CK-18, HOMA-IR, AST Index) was calculated as the product of parameters being significantly different between NAFL and NASH groups. CHAI was significantly higher in NASH (24.2 [15.1-214.0]) compared to either NAFL (15.7 [6.8-22.7]) or control (5.1 [2.4-7.6]) group (p < 0.001) and significantly higher as the severity of steatosis, fibrosis, ballooning, lobular and portal inflammation advanced. CONCLUSION: CHAI was escalating from controls to NAFL and NASH and was higher by increasing the severity of all the main histological lesions. However, a validation study is needed before introducing CHAI in clinical practice.