DSpace Community: Faculdade de Medicina - FM
https://observatorio.fm.usp.br/handle/OPI/23
Faculdade de Medicina - FM2024-03-28T17:18:01ZNon-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
https://observatorio.fm.usp.br/handle/OPI/58624
Title: Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism
Authors: GRANJA, S. C.; LONGATTO-FILHO, A.; CAMPOS, P. B. De; OLIVEIRA, C. P.; STEFANO, J. T.; MARTINS-FILHO, S. N.; CHAGAS, A. L.; HERMAN, P.; D'ALBUQUERQUE, L. C.; ALVARES-DA-SILVA, M. Reis; CARRILHO, F. J.; BALTAZAR, F.; ALVES, V. A. F.
Abstract: Introduction: Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics. Methods: We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed. Results: Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity. Conclusion: Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.2022-01-01T00:00:00ZLung microbiome and origins of the respiratory diseases
https://observatorio.fm.usp.br/handle/OPI/58622
Title: Lung microbiome and origins of the respiratory diseases
Authors: BELIZáRIO, J.; GARAY-MALPARTIDA, M.; FAINTUCH, J.
Abstract: The studies on the composition of the human microbiomes in healthy individuals, its variability in the course of inflammation, infection, antibiotic therapy, diets and different pathological conditions have revealed their intra and inter-kingdom relationships. The lung microbiome comprises of major species members of the phylum Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria and Proteobacteria, which are distributed in ecological niches along nasal cavity, nasopharynx, oropharynx, trachea and in the lungs. Commensal and pathogenic species are maintained in equilibrium as they have strong relationships. Bacterial overgrowth after dysbiosis and/or imbalanced of CD4+ helper T cells, CD8+ cytotoxic T cells and regulatory T cells (Treg) populations can promote lung inflammatory reactions and distress, and consequently acute and chronic respiratory diseases. This review is aimed to summarize the latest advances in resident lung microbiome and its participation in most common pulmonary infections and pneumonia, community-acquired pneumonia (CAP), ventilator-associated pneumonia (VAP), immunodeficiency associated pneumonia, SARS-CoV-2-associated pneumonia, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). We briefly describe physiological and immunological mechanisms that selectively create advantages or disadvantages for relative growth of pathogenic bacterial species in the respiratory tract. At the end, we propose some directions and analytical methods that may facilitate the identification of key genera and species of resident and transient microbes involved in the respiratory diseases’ initiation and progression.2023-01-01T00:00:00ZLiver resection for hepatocellular carcinoma beyond the BCLC: are multinodular disease, portal hypertension, and portal system invasion real contraindications?
https://observatorio.fm.usp.br/handle/OPI/58623
Title: Liver resection for hepatocellular carcinoma beyond the BCLC: are multinodular disease, portal hypertension, and portal system invasion real contraindications?
Authors: BARROS, A. Z. de Almeida; FONSECA, G. M.; KRUGER, J. A. P.; COELHO, F. F.; HERMAN, P.
Abstract: Background: Barcelona Clinic Liver Cancer (BCLC) is a recognized guideline to standardize treatment allocation for hepatocellular carcinoma (HCC); however, many centers criticize its restrictive liver resection recommendations and have published good results after more liberal hepatectomy indications. The objective is to evaluate the results of HCC resection in a single center, with a more liberal indication for resection than proposed by the BCLC guideline. It was performed a retrospective cohort study including all patients who underwent liver resection for HCC in a single center between April 2008 and November 2018. Methods: The results of 150 patients who underwent hepatectomy were evaluated and compared facing both 2010 and 2018 BCLC guidelines. Overall and disease-free survival after resection in patients with none, one, two, or three of the risk factors, as proposed by the BCLC, as contraindications to resection (portal hypertension, portal invasion, and more than one nodule) were analyzed. Results: Nodule size and presence of portal invasion alone did not affect prognosis. If the BCLC 2010 and 2018 guidelines were followed, 46.7% and 26.7% of the patients, respectively, would not have received potentially curative treatment. The median overall and disease-free survival for patients with one BCLC contraindication factor were 43.3 and 15.1 months, respectively. The presence of two risk factors had a negative impact on overall survival (OS) and disease-free survival (DFS), although some patients had long-term survival. The only patient with the three risk factors had a poor outcome. Conclusions: Selected patients with one BCLC contraindication factor may undergo resection with good results, whereas those with two factors should be allocated for hepatectomy only in favorable scenarios. Patients with the three risk factors do not appear to benefit from resection.2022-01-01T00:00:00ZPotential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease
https://observatorio.fm.usp.br/handle/OPI/58621
Title: Potential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease
Authors: FERRARI, J. Tonin; GUERREIRO, G. Tayguara Silveira; LONGO, L.; SILVEIRA, T. R. D.; CERSKI, C. T. Schmidt; TOZAWA, E.; OLIVEIRA, C. P.; ÁLVARES-DA-SILVA, M. R.; URIBE-CRUZ, C.
Abstract: Summary Aim. To evaluate the effects of rifaximin through microbiota modulation in a model of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease. Methods. Three groups of 8 adult male Sprague-Dawley rats each were divided as follows: the HCC group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine as a carcinogen, the hepatocellular carcinoma treated group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine and treated with rifaximin and the control group: animals fed standard diet and water. The rats were euthanized after 16 weeks. We performed analyses of liver pathology for non-alcoholic fatty liver disease severity and cancer grading, gene expression in intestinal and hepatic tissues and fecal microbiota. Results. All animals in the hepatocellular carcinoma group had non-alcoholic fatty liver disease and developed hepatocellular carcinoma lesions. Rifaximin animals showed less intense non-alcoholic fatty liver disease (assessed by non-alcoholic fatty liver disease activity score [NAS]) compared to the hepatocellular carcinoma group. Both the hepatocellular carcinoma and hepatocellular carcinoma + rifaximin groups showed areas of fibrosis as assessed by picrosirius red. Three animals in the rifaximin group did not develop cancerous lesions. Gut microbiota analyses revealed differences in diversity and composition in the control group vs hepatocellular carcinoma and rifaximin groups. Twelve differentially abundant genera were identified between the hepatocellular carcinoma and rifaximin groups. In the rifaximin group, gene expression of intestinal tight junctions decreased. Conclusions. In a rodent model of non-alcoholic fatty liver disease-related hepatocellular carcinoma, rifaximin reduces the histological severity of non-alcoholic fatty liver disease and the occurrence of hepatocellular carcinoma, probably by modulating the gut microbiota independently of markers of intestinal permeability.2023-01-01T00:00:00Z