Atualização das Recomendações da Sociedade Brasileira de Hepatologia para o Tratamento Sistêmico do Carcinoma Hepatocelular / Brazilian society of hepatology updated recommendations for systemic treatment of hepatocellular carcinoma

ABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.

RESUMO O carcinoma hepatocelular (CHC) é uma das principais causas de mortalidade relacionada a câncer no Brasil e no mundo. A Sociedade Brasileira de Hepatologia (SBH) publicou em 2020 a atualização das recomendações da SBH para o diagnóstico e tratamento do CHC. Desde então, novas evidências científicas sobre o tratamento sistêmico do CHC foram relatadas na literatura médica, incluindo novos medicamentos aprovados que não estavam disponíveis na época do último consenso, levando a diretoria da SBH a promover uma reunião monotemática on-line para discutir e rever as recomendações sobre o tratamento sistêmico do CHC. Um grupo de experts foi convidado para realizar uma revisão sistemática da literatura e apresentar uma atualização, baseada em evidências científicas, sobre cada tópico relacionado ao tratamento sistêmico e a apresentar os dados e recomendações resumidas durante a reunião. Todos os painelistas se reuniram para discutir os tópicos e elaborar as recomendações atualizadas. O presente documento é a versão final do manuscrito revisado, contendo as recomendações da SBH, e seu objetivo é auxiliar os profissionais de saúde, formuladores de políticas e planejadores no Brasil e na América Latina na tomada de decisões sobre o tratamento sistêmico de pacientes com CHC.

Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series

Abstract Objective: 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 São Paulo, at the Faculdade de Medicina da Universidade de São 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.

Management of hepatocellular carcinoma during the COVID-19 pandemic - São Paulo Clínicas liver cancer group multidisciplinary consensus statement

More than 18 million people in 188 countries have been diagnosed as having coronavirus disease (COVID-19), and COVID-19 has been responsible for more than 600,000 deaths worldwide. Brazil is now the second most affected country globally. Faced with this scenario, various public health measures and changes in the daily routines of hospitals were implemented to stop the pandemic. Patients with hepatocellular carcinoma (HCC) are at an increased risk for severe COVID-19 as they present with two major diseases: cancer and concomitant chronic liver disease. The COVID-19 pandemic can significantly impact the management of HCC patients from diagnosis to treatment strategies. These patients need special attention and assistance at this time, especially since treatment for tumors cannot be delayed in most cases. The aim of this guideline was to standardize the management of HCC patients during the COVID-19 pandemic. This document was developed, on the basis of the best evidence available, by a multidisciplinary team from Instituto do Câncer do Estado de São Paulo (ICESP), and Instituto Central of the Hospital das Clínicas da Universidade de São Paulo (HC-FMUSP), which are members of the São Paulo Clínicas Liver Cancer Group.

Adherence to BCLC recommendations for the treatment of hepatocellular carcinoma: impact on survival according to stage

OBJECTIVES: This study sought to assess the adherence of newly diagnosed hepatocellular carcinoma patients to the Barcelona Clinic Liver Cancer system treatment guidelines and to examine the impact of adherence on the survival of patients in different stages of the disease. METHODS: This study included all patients referred for the treatment of hepatocellular carcinoma between 2010 and 2012. Patients (n=364) were classified according to the Barcelona Clinic Liver Cancer guidelines. Deviations from the recommended guidelines were discussed, and treatment was determined by a multidisciplinary team. The overall survival curves were estimated with the Kaplan-Meier method and were compared using the log-rank test. RESULTS: The overall rate of adherence to the guidelines was 52%. The rate of adherence of patients in each scoring group varied as follows: stage 0, 33%; stage A, 45%; stage B, 78%; stage C, 35%; and stage D, 67%. In stage 0/A, adherent patients had a significantly better overall survival than non-adherent patients (hazard ratio=0.19, 95% confidence interval (CI): 0.09-0.42; p<0.001). Among the stage D patients, the overall survival rate was worse in adherent patients than in non-adherent patients (hazard ratio=4.0, 95% CI: 1.67-9.88; p<0.001), whereas no differences were observed in patients in stages B or C. CONCLUSIONS: The rate of adherence to the Barcelona Clinic Liver Cancer staging system in clinical practice varies according to clinical disease stage. Adherence to the recommended guidelines positively impacts survival, especially in patients with early-stage disease.

The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib

ABSTRACT Background and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database. Results. Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.

Clinical and pathological evaluation of fibrolamellar hepatocellular carcinoma: a single center study of 21 cases

OBJECTIVES: Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor that differs from conventional hepatocellular carcinoma in several aspects. The aim of this study was to describe the clinical, surgical and histopathological features of fibrolamellar hepatocellular carcinoma and to analyze the factors associated with survival. METHODS: We identified 21 patients with histopathologically diagnosed fibrolamellar hepatocellular carcinoma over a 22-year period. Clinical information was collected from medical records and biopsies, and surgical specimens were reviewed. RESULTS: The median age at diagnosis was 20 years. Most patients were female (67%) and did not have associated chronic liver disease. Most patients had a single nodule, and the median tumor size was 120 mm. Vascular invasion was present in 31% of patients, and extra-hepatic metastases were present in 53%. Fourteen patients underwent surgery as the first-line therapy, three received chemotherapy, and four received palliative care. Eighteen patients had “pure fibrolamellar hepatocellular carcinoma,” whereas three had a distinct area of conventional hepatocellular carcinoma and were classified as having “mixed fibrolamellar hepatocellular carcinoma.” The median overall survival was 36 months. The presence of “mixed fibrolamellar hepatocellular carcinoma” and macrovascular invasion were predictors of poor survival. Vascular invasion was associated with an increased risk of recurrence in patients who underwent surgery. CONCLUSION: Fibrolamellar hepatocellular carcinoma was more common in young female patients without chronic liver disease. Surgery was the first therapeutic option to achieve disease control, even in advanced cases. Vascular invasion was a risk factor for tumor recurrence. The presence of macrovascular invasion and areas of conventional hepatocellular carcinoma were directly related to poor survival. .

Use of serological techniques for determination of Spodoptera frugiperda (J E Smith) predators (Lepidoptera: Noctuidae)

Spodoptera frugiperda (J E Smith) is an important pest of several crops, but especially on maize in Brazil. The implementation of biological control measures hinges on the identification of its predators and other natural enemies. As a means of identifying predators, antibodies against S. frugiperda eggs were generated by inoculating rabbits with macerated S. frugiperda eggs, and the production of antibodies against S. frugiperda egg proteins was verifi ed by double immunodiffusion (DID). These antibodies were then utilized in another serological technique, counterimmunoeletrophoresis (CIE), to identify insects that could have ingested S. frugiperda eggs. Macerates of entire insects collected in maize plantations and of individual parts of their digestive tract, including the crop, were the source of antigens in the CIE, while predators fed S. frugiperda eggs in the laboratory served as the control. Antibodies produced by the inoculated rabbits were effective in detecting S. frugiperda egg proteins, especially if crop macerates were used as antigens. Among the species of insects collected from maize plantations, Lagria villosa Fabricius (Coleoptera: Lagriidae) and a species of Lygaeidae (Hemiptera) were identified as possible S. frugiperda predators.

Influência do método Reequilíbrio Toracoabdominal sobre a força muscular respiratória de pacientes com fibrose cística / Influence of the technique of re-educating thoracic and abdominal muscles on respiratory muscle strength in patients with cystic fibrosis

OBJETIVO: Avaliar o efeito do método Reequilíbrio Toracoabdominal na força dos músculos respiratórios de pacientes com fibrose cística, acompanhados no Ambulatório de Fibrose Cística da Universidade Católica de Brasília. MÉTODOS: A amostra, constituída de 29 fibrocísticos, foi caracterizada com base em dados antropométricos, genéticos e de colonização bacteriana. Espirometria, manovacuometria e antropometria foram realizadas antes e depois do tratamento fisioterapêutico, no qual se utilizou o método Reequilíbrio Toracoabdominal, duas vezes por semana, durante quatro meses. RESULTADOS: Houve aumento da pressão inspiratória máxima e da pressão expiratória máxima após o tratamento fisioterapêutico em todos os pacientes, naqueles sem distúrbio ventilatório obstrutivo e naqueles com distúrbio ventilatório obstrutivo leve (p < 0,05). Foi encontrada correlação positiva entre a idade e a pressão expiratória máxima para a maioria dos grupos. A pressão inspiratória máxima só apresentou correlação positiva com a idade no grupo com distúrbio ventilatório obstrutivo leve (p = 0,012; r = 0,817). Para o sexo feminino e para o grupo sem distúrbio ventilatório obstrutivo houve correlação negativa entre a pressão expiratória máxima e a colonização por Pseudomonas aeruginosa (p = 0,036; r = -0,585). CONCLUSÃO: Para os fibrocísticos avaliados, o método Reequilíbrio Toracoabdominal aumentou a força dos músculos respiratórios, o que reafirma a importância do tratamento fisioterapêutico para estes pacientes.