VENANCIO AVANCINI FERREIRA ALVES
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina - Líder
14 resultados
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- Understanding Sabia virus infections (Brazilian mammarenavirus)(2022) NASTRI, Ana Catharina; DUARTE-NETO, Amaro Nunes; CASADIO, Luciana Vilas Boas; SOUZA, William Marciel de; CLARO, Ingra M.; MANULI, Erika R.; SELEGATTO, Gloria; SALOMA, Matias C.; FIALKOVITZ, Gabriel; TABORDA, Mariane; ALMEIDA, Bianca Leal de; MAGRI, Marcello C.; GUEDES, Ana Rubia; NETO, Laura Vieira Perdigao; SATAKI, Fatima Mitie; GUIMARAES, Thais; MENDES-CORREA, Maria Cassia; TOZETTO-MENDOZA, Tania R.; FUMAGALLI, Marcilio Jorge; HO, Yeh-Li; SILVA, Camila ALves Maia da; COLETTI, Thais M.; JESUS, Jacqueline Goes de; ROMANO, Camila M.; HILL, Sarah C.; PYBUS, Oliver; PINHO, Joao Renato Rebello; LEDESMA, Felipe Lourenco; CASAL, Yuri R.; KANAMURA, Cristina; ARAUJO, Leonardo Jose Tadeu de; FERREIRA, Camila Santos da Silva; GUERRA, Juliana Mariotti; FIGUEIREDO, Luiz Tadeu Moraes; DOLHNIKOFF, Marisa; FARIA, Nuno R.; SABINO, Ester C.; AVANCINI, Venacio; ALVES, Ferreira; LEVIN, Anna S.Background: Only two naturally occurring human Sabi ' a virus (SABV) infections have been reported, and those occurred over 20 years ago. Methods: We diagnosed two new cases of SABV infection using metagenomics in patients thought to have severe yellow fever and described new features of histopathological findings. Results: We characterized clinical manifestations, histopathology and analyzed possible nosocomial transmission. Patients presented with hepatitis, bleeding, neurological alterations and died. We traced twenty-nine hospital contacts and evaluated them clinically and by RT-PCR and neutralizing antibodies. Autopsies uncovered unique features on electron microscopy, such as hepatocyte ""pinewood knot"" lesions. Although previous reports with similar New-World arenavirus had nosocomial transmission, our data did not find any case in contact tracing. Conclusions: Although an apparent by rare, Brazilian mammarenavirus infection is an etiology for acute hemorrhagic fever syndrome. The two fatal cases had peculiar histopathological findings not previously described. The virological diagnosis was possible only by contemporary techniques such as metagenomic assays. We found no subsequent infections when we used serological and molecular tests to evaluate close contacts.
- IMMUNOHISTOCHEMICAL ASSESSMENT OF LYMPHATIC VESSELS IN HUMAN LIVERS WITH CHRONIC HEPATITIS C - RELATION TO HISTOLOGICAL VARIABLES(2022) ASSATO, Aline Kawassaki; PASINATO, Ana Paula Beltrame Farina; CIRQUEIRA, Cinthya dos Santos; WAKAMATSU, Alda; ALVES, Venâncio Avancini FerreiraABSTRACT Background Viral hepatitis C is a significant public health challenge. The disease may remain clinically silent in both acute and chronic forms, and chronic infections may progress to advanced disease such as cirrhosis and hepatocellular carcinoma, requiring costly treatment, compromising the patient’s quality of life and even leading to death. For this reason, it is one of the most frequent indications for liver transplantation. Although treatment with direct-acting antivirals represents remarkable progress, many patients are still infected and even those who cleared the viral infection must be followed due to their previous hepatic lesions, especially regarding the disturbances of lobular architecture and the sanguineal and lymphatic vessels. Objective To assess immunohistochemical aspects of lymphatic sprouts and mature lymphatic vascularity with histological variables of liver injury attributable to hepatitis C virus (HCV) and fatty disease. Methods The present study included 72 liver biopsies of cases with chronic hepatitis C. Morphologic changes reflecting “staging” and “activity” were analyzed. Immunohistochemical reactions were performed with monoclonal antibody D2-40 anti-podoplanin. Major histological variables were also semiquantified so as to enable the search for possible associations among histological and Immunohistochemical criteria, as well as with genotypes 1 and 3 of HCV. Results Histological findings showed that the different degrees of strutural changes were well represented in this casuistic. Intralobular/parenchymal necro-inflammatory activity was predominantly mild to moderate. Most cases did not show major evidences of fatty disease, which was found significantly higher in cases infected with HCV genotype 3. The amount of portal lymphatic sprouts increased along with the progression of structural changes, maximal at cirrhosis. Portal lymphatic sprouts as well as portal mature lymphatic vessels also showed an increase parallel to the increase in the degree of portal/septal inflammatory infiltrate. In the present study, no significant association was found between the proportion of portal lymphatic sprouts or portal mature lymphatic vessels and the degree of periportal/periseptal activity. No significant relations were detected between lymphatic sprouts/mature vessels and periportal or parenchymal inflammatory activity, nor with infections due to HCV genotype 1 or 3. Conclusion Visualization and semiquantitation of sprouts and mature lymphatic vessels were clearly yielded by Immunohistochemical staining with monoclonal antibody D2-40. The amount of lymphatics was increased along fibrogenic process, significantly related to progression of liver disease and maximal at cirrhosis. No significant relations were detected with necro-inflammatory activity at interface or in the parenchyma.
- Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence(2022) PINHO, Mariana P.; LEPSKI, Guilherme A.; REHDER, Roberta; CHAUCA-TORRES, Nadia E.; EVANGELISTA, Gabriela C. M.; TEIXEIRA, Sarah F.; FLATOW, Elizabeth A.; OLIVEIRA, Jaqueline V. de; FOGOLIN, Carla S.; PERES, Nataly; AREVALO, Analia; ALVES, Venancio; BARBUTO, Jose A. M.; BERGAMI-SANTOS, Patricia C.Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic-tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.
- Liver disease accompanied by enteropathy in common variable immunodeficiency: Common pathophysiological mechanisms(2022) LIMA, Fabiana Mascarenhas Souza; TOLEDO-BARROS, Myrthes; ALVES, Venancio Avancini Ferreira; DUARTE, Maria Irma Seixas; TAKAKURA, Cleusa; BERNARDES-SILVA, Carlos Felipe; MARINHO, Ana Karolina Barreto Berselli; GRECCO, Octavio; KALIL, Jorge; KOKRON, Cristina MariaCommon variable immunodeficiency (CVID) is one of the inborn errors of immunity that have the greatest clinical impact. Rates of morbidity and mortality are higher in patients with CVID who develop liver disease than in those who do not. The main liver disorder in CVID is nodular regenerative hyperplasia (NRH), the cause of which remains unclear and for which there is as yet no treatment. The etiology of liver disease in CVID is determined by analyzing the liver injury and the associated conditions. The objective of this study was to compare CVID patients with and without liver-spleen axis abnormalities in terms of clinical characteristics, as well as to analyze liver and duodenal biopsies from those with portal hypertension (PH), to elucidate the pathophysiology of liver injury. Patients were divided into three groups: Those with liver disease/PH, those with isolated splenomegaly, and those without liver-spleen axis abnormalities. Clinical and biochemical data were collected. Among 141 CVID patients, 46 (32.6%) had liver disease/PH; 27 (19.1%) had isolated splenomegaly; and 68 (48.2%) had no liver-spleen axis abnormalities. Among the liver disease/PH group, patients, even those with mild or no biochemical changes, had clinical manifestations of PH, mainly splenomegaly, thrombocytopenia, and esophageal varices. Duodenal celiac pattern was found to correlate with PH (p < 0.001). We identified NRH in the livers of all patients with PH (n = 11). Lymphocytic infiltration into the duodenal mucosa also correlated with PH. Electron microscopy of liver biopsy specimens showed varying degrees of lymphocytic infiltration and hepatocyte degeneration, which is a probable mechanism of lymphocyte-mediated cytotoxicity against hepatocytes and enterocytes. In comparison with the CVID patients without PH, those with PH were more likely to have lymphadenopathy (p < 0.001), elevated beta(2)-microglobulin (p < 0.001), low B-lymphocyte counts (p < 0.05), and low natural killer-lymphocyte counts (p < 0.05). In CVID patients, liver disease/PH is common and regular imaging follow-up is necessary. These patients have a distinct immunological phenotype that may predispose to liver and duodenal injury from lymphocyte-mediated cytotoxicity. Further studies could elucidate the cause of this immune-mediated mechanism and its treatment options.
- Prognostic implications of tumor-infiltrating lymphocytes in association with programmed cell death ligand 1 expression in remnant gastric cancer(2022) PEREIRA, Marina Alessandra; RAMOS, Marcus Fernando Kodama Pertille; DIAS, Andre Roncon; CARDILI, Leonardo; MORAES, Rafael Dyer Rodrigues de; RIBEIRO, Renan Ribeiro E.; ALVES, Venancio Avancini Ferreira; ZILBERSTEIN, Bruno; MELLO, Evandro Sobroza de; JR, Ulysses RibeiroObjective: Remnant gastric cancer (RGC) is usually associated with a worse prognosis. As they are less common and very heterogeneous tumors, new prognostic and reliable determinants are required to predict patients' clinical course for RGC. This study aimed to investigate the tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) status as prognostic biomarkers in a cohort of patients with RGC to develop an immune -related score.Methods: Patients with gastric cancer (GC) who underwent curative intent gastrectomy were retrospectively investigated. RGC resections with histological diagnosis of gastric adenocarcinoma were enrolled in the study. The risk score based on immune parameters was developed using binary logistic regression analysis. RGCs were divided into high-risk (HR), intermediate-risk (IR), and low-risk (LR) groups based on their immune score. The markers (CD3+, CD4+/CD8+ T cells and PD-L1) were selected for their potential prognostic, therapeutic value, and evaluated by immunohistochemistry (IHC).Results: A total of 42 patients with RGC were enrolled in the study. The score based on immune parameters exhibited an accuracy of 79% [the area under the receiver operating characteristic curve (AUC)=0.79, 95% confidence interval (95% CI), 0.63-0.94, P=0.002], and the population was divided into 3 prognostic groups: 10 (23.8%) patients were classified as LR, 15 (35.7%) as IR, and 17 (40.5%) as HR groups. There were no differences in clinicopathological and surgical characteristics between the three groups. In survival analysis, HR and IR groups had worse disease-free survival and overall survival rates compared to the LR group. In the multivariate analysis, lymph node metastasis and the immune score risk groups were independent factors related to worse survival.Conclusions: A scoring system with immune-related markers was able to distinguish prognostic groups of RGC associated with survival. Accordingly, tumor-infiltrating immune lymphocytes and PD-L1 status may serve as a potential prognostic biomarker for patients with RGC.
- Searching for SARS-CoV-2 in Cancer Tissues: Results of an Extensive Methodologic Approach based on ACE2 and Furin Expression(2022) RICARDO, Sara; CANAO, Pedro; MARTINS, Diana; MAGALHAES, Ana C.; PEREIRA, Marina; RIBEIRO-JUNIOR, Ulysses; MELLO, Evandro Sobroza de; ALVES, Venancio A.; PINTO, Regina; LEITAO, Dina; ALVES, Georgina; OLIVEIRA, Rute; WILTON, Joana; COSTELHA, Susete; MEIRELES, Diana; CABANES, Didier; DAVID, Leonor; SCHMITT, FernandoSimple Summary SARS-CoV-2 is the virus that causes COVD-19; there is consensus that this virus infects cells presenting the angiotensin-converting enzyme 2 (ACE2) receptor at the cell surface. In our study, we assessed the expression profiles of cancer cells regarding the expressions of ACE2 and furin (another important player in the infection process). We analyzed a series of formalin-fixed paraffin-embedded samples of tumor tissues from cancer patients who underwent surgery at the beginning of the pandemic, including some cases with known positive results for SARS-CoV-2. Our goal was to explore the possibility of viral infections in cancer tissues by detecting viral RNA and/or proteins using histology-based methods. From this extensive methodologic approach, we show that colon and gastric carcinoma cells present high expression levels of ACE2 and furin, contrasting with a negative expression profile of ACE2 in thyroid carcinoma. Some cases tested positive for SARS-CoV-2 by PCR extracted from tissue sections, but in situ hybridization and immunohistochemistry did not show consistent results of a viral presence in the cancer cells. Our study raises the possibility of ACE2-mediated viral tropism for cancer tissues to be clarified in future studies. SARS-CoV-2 pandemics have been massively characterized on a global scale by the rapid generation of in-depth genomic information. The main entry gate of SARS-CoV-2 in human cells is the angiotensin-converting enzyme 2 (ACE2) receptor. The expression of this protein has been reported in several human tissues, suggesting a correlation between SARS-CoV-2 organotropism and ACE2 distribution. In this study, we selected (a series of) 90 patients who were submitted to surgery for tumor removal between the beginning of the SARS-CoV-2 pandemic and the closure of operating rooms (by the end of March 2020) in two different countries-Portugal and Brazil. We evaluated the expressions of ACE2 and furin (another important factor for virus internalization) in colon (n = 60), gastric (n = 19), and thyroid (n = 11) carcinomas. In a subseries of cases with PCR results for SARS-CoV-2 detection in the peri-operatory window (n = 18), we performed different methodological approaches for viral detections in patient tumor samples. Our results show that colon and gastric carcinomas display favorable microenvironments to SARS-CoV-2 tropism, presenting high expression levels of ACE2 and furin. From the subseries of 18 cases, 11 tested positive via PCR detection performed in tumor blocks; however, a direct association between the ACE2 expression and SARS-CoV-2 infection was not demonstrated in cancer cells using histology-based techniques, such as immunohistochemistry or in situ hybridization. This study raises the possibility of ACE2-mediated viral tropism in cancer tissues to be clarified in future studies.
- Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series(2022) ALENCAR, Regiane Saraiva de Souza Melo; OLIVEIRA, Claudia P.; CHAGAS, Aline Lopes; FONSECA, Leonardo Gomes da; MACCALI, Claudia; SAUD, Lisa Rodrigues da Cunha; XERFAN, Mariana Pinheiro; STEFANO, Jose Tadeu; HERMAN, Paulo; D'ALBUQUERQUE, Luiz Augusto Carneiro; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JoseObjective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de Sao Paulo, at the Faculdade de Medicina da Universidade de Sao Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. Results: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C-D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.
- Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence(2022) FONSECA, Leonardo G. Da; HASHIZUME, Pedro H.; OLIVEIRA, Irai Santana de; IZQUIERDO-SANCHEZ, Laura; SAUD, Lisa Rodrigues da Cunha; XERFAN, Mariana Pinheiro; ALVES, Venancio Avancini Ferreira; MELLO, Evandro Sobroza de; HERMAN, Paulo; BANALES, Jesus M.; OLIVEIRA, Claudia P.; CARRILHO, Flair J.Simple Summary A potential relationship between cholangiocarcinoma and metabolic disorders has been suggested, but there is a lack of published data. This study aimed to describe the prevalence of metabolic disorders in a cohort of 122 patients with cholangiocarcinoma and report clinical outcomes. We found a prevalence of 42.6% of metabolic disorders. There was no significant difference in overall survival between patients with or without metabolic disorders, although there was a better survival in the subgroup of patients undergoing surgical resection. This indicates a need to better explore the association between cholangiocarcinoma in a metabolic background. Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (""metabolic disorder group"") and (2) without any of these features (""non-metabolic-disorder group""). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1-17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The ""metabolic disorder group"" (n = 52) had a median survival of 15.5 months (95% CI 10.9-33.9) vs. 11.5 months (95% CI 8.4-16.5) in the ""non-metabolic-disorder group"" (n = 70) (HR: 1.10; 95% CI 0.62-1.94). Patients with resectable disease in the ""metabolic group"" had longer survival than patients in the ""non-metabolic group"" (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6-26.9); HR = 0.12, 95% CI 0.03-0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background.
- Phylogeographic patterns of the yellow fever virus around the metropolitan region of Sao Paulo, Brazil, 2016-2019(2022) CUNHA, Marielton dos Passos; DUARTE-NETO, Amaro Nunes; POUR, Shahab Zaki; PEREIRA, Barbara Brito de Souza; HO, Yeh-Li; PERONDI, Beatriz; SZTAJNBOK, Jaques; ALVES, Venancio Avancini Ferreira; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; SALDIVA, Paulo Hilario Nascimento; ZANOTTO, Paolo Marinho de AndradeFrom 2016 to 2019, the largest outbreak caused by the Yellow Fever virus (YFV) in the 21(st) century in the Americas occurred in southeastern Brazil. A sylvatic cycle of transmission was reported near densely populated areas, such as the large metropolitan area of the city of Sao Paulo. Here, we describe the origin, spread, and movement of the YFV throughout the state of Sao Paulo. Whole-genome sequences were obtained from tissues of two patients who died due to severe yellow fever, during 2018-2019. Molecular analysis indicated that all analyzed tissues were positive for YFV RNA, with the liver being the organ with the highest amount of viral RNA. Sequence analysis indicates that genomes belonged to the South American genotype I and were grouped in the epidemic clade II, which includes sequences from the states of Goias, Minas Gerais, and Sao Paulo of previous years. The analysis of viral dispersion indicates that the outbreak originated in Goias at the end of 2014 and reached the state of Sao Paulo through the state of Minas Gerais after 2016. When the virus reached near the urban area, it spread towards both the east and south regions of the state, not establishing an urban transmission cycle in the metropolitan region of Sao Paulo. The virus that moved towards the east met with YFV coming from the south of the state of Rio de Janeiro, and the YFV that was carried to the south reached the Brazilian states located in the south region of the country.
- Histopathological factors versus margin size in single colorectal liver metastases: Does a 1-cm margin size matter?(2022) FONSECA, Gilton M.; MELLO, Evandro S. de; FARAJ, Sheila F.; KRUGER, Jaime A. P.; JEISMANN, Vagner B.; COELHO, Fabricio F.; ALVES, Venancio A. F.; HERMAN, PauloBackground and objective: The ideal margin width for surgical resection of colorectal liver metastases has been extensively studied, but not sufficiently in accordance with other pathological factors. The aim of this study was to assess for the first time the prognostic impact of margin widths according to different prognostic pathological factors in colorectal liver metastasis. Methods: We evaluated 101 patients with a single resected metastasis. Slides stained by HE were assessed for the presence of poorly differentiated clusters, peritumoral inflammatory infiltrate, tumor pseudocapsule, and tumor borders pattern. Overall survival, disease-free survival, and hepatic recurrence were evaluated. The pathologic factors prognostic impact was evaluated according to a (< or >) 10-mm margin size. Results: Factors independently associated with a shorter overall survival were absence of tumor pseudocapsule (p < 0.001) and infiltrative tumor border pattern (p = 0.019). The absence of tumor pseudocapsule was the only factor independently associated with shorter disease-free survival (p < 0.001). Hepatic recurrence was associated with infiltrative tumor border and absence of pseudocapsule. Margin width > 10 mm did not impact overall survival independently of the studied histological prognostic factors. Conclusions: In colorectal liver metastasis resection, the absence of tumor pseudocapsule was significantly associated with shorter overall survival and disease-free survival and hepatic recurrence. However, margins larger than 10 mm did not offer survival benefit when other pathologic negative prognostic factors were concomitantly analyzed, reinforcing the idea that biology, rather than margin size, is crucial for prognosis.