Experience with Sorafenib in 3 Hospitals in Sao Paulo.

INTRODUCTION AND AIM: Sorafenib has been the standard of care for first-line treatment of advanced hepatocellular carcinoma, a complex disease that affects an extremely heterogenous population. Thereby requiring multidisciplinary individualized treatment strategies that match the disease characteristics and the patients' specific needs. MATERIAL AND METHODS: Data for 175 patients who received sorafenib for hepatocellular carcinoma in three different hospitals in Sao Paulo, Brazil over a span of nine years were retrospectively analyzed. RESULTS: The median age was 62 years. Percentages of patients with Child-Pugh A, B and C liver cirrhosis were 61%, 31% and 5%, respectively. Approximately half of the patients had Barcelona Clinic Liver Cancer stage B disease, and the other half had stage C. The median treatment duration was 253 days. Sorafenib dose was reduced to 400 mg/day in 41% of the patients due to toxicity. Overall objective response rate as per Response Evaluation Criteria in Solid Tumors and its modified version was 39%. Patients who received transarterial chemoembolization (TACE) at any point during sorafenib therapy were significantly more likely to experience an objective response. After a median follow-up of 339 days, the median overall survival was 380 days. Child-Pugh cirrhosis, tumor response and concomitant chemoembolization were independent prognostic factors for overall survival in multivariate analysis. CONCLUSION: Our results suggest that, in experienced hands, sorafenib therapy may benefit carefully selected hepatocellular carcinoma patients for whom other therapies are initially contraindicated, including those patients with Child-Pugh B liver function and those patients who are subsequently treated with concomitant TACE.

Advanced hepatocellular carcinoma. Review of targeted molecular drugs.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world in terms of incidence, accounting for approximately 630 thousand new cases per year; in addition, HCC is the third most common cause of cancer death. Worldwide, the greatest risk factors for HCC are the infections caused by hepatitis B and C viruses, which increase the risk of developing the disease by about 20 times. The standard treatment in the early stages of the disease, such as surgical resection, local ablation and liver transplantation, are able to cure a proportion of patients, but most cases of HCC present in advanced stages, precluding the use of such treatments with curative intent. In these advanced stages, systemic treatments are commonly used. Unfortunately, chemotherapy with conventional cytotoxic agents is ineffective and does not seem to modify the natural history of disease. Treatment options for patients with advanced HCC are extremely limited, but the identification of signaling pathways, and the recognition of the role of these pathways in the pathogenesis of the disease resulted in the development of drugs directed at specific therapeutic targets. One such drug is Sorafenib, a kinase inhibitor with antiangiogenic and antiproliferative properties. In conclusion, Sorafenib has demonstrated survival benefits in patients with advanced HCC, thus representing a new standard reference for systemic treatment in these cases.

Use of AST platelet ratio index (APRI Score) as an alternative to liver biopsy for treatment indication in chronic hepatitis C.

Chronic hepatitis C (CHC) is one of the most important causes of chronic liver disease in the world, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Liver biopsy is currently performed before therapy indication. Although, it is the golden standard there are many reasons to avoid or delay the procedure. APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C (CHC). The rationale of this study was to observe the accuracy of APRI Score in comparison to liver biopsy in 400 patients divided into two groups of 200 carriers (Validation and Experimental groups respectively) selected at random or according to liver fibrosis staging (METAVIR). The ROC curves showed a concordance among these two methods of 92% and 88.5% when 1.05 was the cut off (F3 and F4), and 87% and 83%, on 0.75 cut offs (F2-F4). The discordance in advanced fibrosis staging (F3 and F4) was only 16 (8%) and 22 (11%) out of 200 patients in the experimental and validation groups, respectively. In 26 (13%) out of 200 patients in the experimental group and 34 (17%) out of 200 patients in the validation group, there was discordance between APRI Score and liver biopsy in moderate and advanced fibrosis (F2-F4). In conclusion APRI is a serological marker that has satisfactory sensitivity and specificity together with a high predictive value and it can be useful either in the absence of a biopsy or to reduce the frequency with which biopsies need to be carried out to monitor the evolution of chronic hepatitis C and the right moment for treatment indication.

Cardiac morphofunctional injuries in patients with hepatitis C virus: doppler echocardiographic evaluation.

OBJECTIVE: To evaluate the possible morphological and functional heart injuries in hepatitis C virus patients. METHODS: Control-case study analyzing Doppler echocardiographic aspects in 31 hepatitis C virus patients and 20 controls. RESULTS: There were no significant difference in relation to the myocardial thickening, left ventricular diameters, circumferential shortening, ejection fraction, mitral valve flow velocities, tissue sistolic and diastolic mitral annular ones. CONCLUSION: Individuals with hepatitis C virus in the initial phases of the disease did not show morpho-functional abnormalities of the heart when evaluated by Doppler echocardiography.

O coração em portadores do vírus da hepatite C: avaliação Dopplerecocardiográfica / Cardiac morphofunctional injuries in patients with hepatitis C virus: doppler echocardiographic evaluation

OBJETIVO: Avaliar possíveis alterações morfofuncionais cardíacas em portadores crônicos do vírus da hepatite C pela Dopplerecocardiografia. MÉTODOS: Estudo observacional caso-controle com análise de parâmetros Dopplerecocardiográficos de 31 pacientes portadores crônicos do vírus da hepatite C numa fase não avançada da doença, diagnosticados por biópsia (sem cirrose, carcinoma hepatocelular ou disfunção hepática) e 20 casos-controle. RESULTADOS: Não houve diferenças estatisticamente significantes da espessura parietal, diâmetros cavitários, fração de ejeção, encurtamento circunferencial e nas velocidades de fluxo mitral e teciduais sistólica e diastólica do anel mitral entre os dois grupos estudados. CONCLUSÃO: Nas fases não avançadas, portadores do vírus da hepatite C não apresentaram alterações morfo-funcionais cardíacas, sob análise do ventrículo esquerdo.

OBJECTIVE: To evaluate the possible morphological and functional heart injuries in hepatitis C virus patients. METHODS: Control-case study analyzing Doppler echocardiographic aspects in 31 hepatitis C virus patients and 20 controls. RESULTS: There were no significant difference in relation to the myocardial thickening, left ventricular diameters, circumferential shortening, ejection fraction, mitral valve flow velocities, tissue sistolic and diastolic mitral annular ones. CONCLUSION: Individuals with hepatitis C virus in the initial phases of the disease did not show morpho-functional abnormalities of the heart when evaluated by doppler echocardiography.

Predição da coledocolitíase pela associação de indicadores clínicos e laboratoriais em dois momentos do pré-operatório da colecistectomia / Prediction of preoperative choledocholithiasis by the association of clinical and laboratory indicators in two distinct moments

OBJETIVO: O propósito deste estudo foi determinar a probabilidade de ocorrência de coledocolitíase através do estudo da associação de indicadores clínicos e laboratoriais desta doença em dois momentos do pré-operatório de colecistectomia. MÉTODO: Entre março de 2001 e março de 2002, 48 pacientes consecutivos com colelitíase foram submetidos a colecistectomia e colangiografia intra-operatória (CIO). Os pacientes foram divididos em dois grupos, sendo o grupo A constituído por 13 pacientes com coledocolitíase e o grupo B por 35 pacientes sem esta doença. Os pacientes foram investigados quanto aos indicadores clínicos e laboratoriais da coledocolitíase, analisados em dois períodos, tomando como ponto de corte as 48 horas que precederam a cirurgia. Posteriormente, estes indicadores pré-operatórios foram associados na equação da regressão logística em diferentes combinações. RESULTADOS: Utilizando a equação da regressão logística, constatou-se que a associação de dois indicadores clínicos em ambos os períodos (icterícia e sinal de Murphy) e dois laboratoriais ( nível de corte da gama glutamil transpeptidase e bilirrubina direta 48 horas antes da cirurgia) foi a mais adequada para a predição da coledocolitíase. Os valores obtidos por esta equação mostraram concordância com os grupos A e B, de 95,6 por cento, e discordância de 4,4 por cento (p= 0,0000007 e k = 0,89). Esta equação mostrou sensibilidade de 92,3 por cento, especificidade de 97,0 por cento, valor preditivo positivo de 92,3 por cento e valor preditivo negativo de 97 por cento. Estes valores foram próximos aos obtidos pela CIO, que mostrou concordância com os grupos estudados de 95,8 por cento, e discordância de 4,2 por cento (k = 0,90). CONCLUSÃO: Considerando os resultados obtidos, recomenda-se a associação de indicadores da coledocolitíase na equação da regressão logística para estabelecer a probabilidade de ocorrer coledocolitíase associada à colelitíase. A utilização desta equação...

BACKGROUND: The purpose of this study was to determine the probability of choledocholithiasis from the association of clinical and laboratory indicators at two moments of the preoperative phase of cholecystectomy. METHODS: Between March 2001 and March 2002, 48 consecutive patients with cholelithiasis were submitted to cholecystectomy and intra-operative cholangiography (IOC). The patients were divided into two groups, with group A composed of 13 patients with choledocholithiasis and group B of 35 patients without this disease. They were investigated by clinical and laboratory indicators of choledocholithiasis, analyzed in two periods, taking as the cut point the 48 hours that preceded the surgery. Later on, these preoperative indicators were associated in the logistic regression equation in different combinations. RESULTS: Using the logistic regression equation, it was found that the association of two clinical indicators in both periods (jaundice and Murphyæs sign) and two laboratory indicators (the cut level of gamma glutamyl transpeptidase and direct bilirubin 48 hours before the surgery) was the most suitable for predicting choledocholithiasis. The values obtained by this equation showed an agreement with groups A and B of 95.6 percent, and a disagreement of 4.4 percent (p= 0.0000007 and k = 0.89). This equation showed sensitivity of 92.3 percent, specificity of 97.0 percent, a positive predictive value of 92.3 percent and a negative predictive value of 97 percent. These values were close to those obtained by the CIO, which showed agreement with the groups studied of 95.8 percent, and disagreement of 4.2 percent (k = 0.90). CONCLUSION: The association of indicators of choledocholithiasis is recommended to establish the probability of there occurring choledocholithiasis associated with cholelithiasis. The use of this equation may provide better guidance for the diagnostic and therapeutic handling of this disease.

Strongyloides hyperinfection simulating inflammatory bowel disease

Strongyloides stercoralis infection may present with acute gastrointestinal symptoms or persist for many years in the asymptomatic, immunocompetent host. Hyperinfection usually occurs as a result of an alteration in immune status. The authors report three cases of Strongyloides hyperinfection that presented as diarrhea and weight loss and the colonoscopy revealed either ulcerative colitis or pancolitis. One of them had a fatal outcome. The screening for this infection is mandatory for patients in endemic areas with a history of diarrhea, as an early diagnosis and therapy can have marked impact on the outcome of the disease.

Reagudização de hepatite B crônica associada à quimioterapia e neoplasias hematológicas: relato de três casos e revisão de literatura / Chronic hepatitis B flares associated to chemotherapy and hematological neoplasms: report of three cases and literature review

Existem cerca de 350 milhões de pessoas infectadas pelo VHB em todo mundo.As reagudizações fazem parte da história natural da hepatite B e são causadas por vários fatores, alguns identificáveis e potencialmente tratáveis. as exacerbações do VHB são frequentes após uso de imunossupressores, quimioterápicos e corticosteróides, podendo evoluir desde formas assintomáticas até fulminantes com óbito. O reconhecimento de pacientes com alto risco de apresentar reagudizações é importante, pois estes devem ser monitorados e receber tratamento antiviral adequado. Relatam-se três casos de exacervações do HVB em portadores de neoplasias hematológicas com evoluções distintas. O objetivo é mostrar a importância do reconheciemnto precoce de exacerbações da hepatite B crônica em pacientes que serão submetidos a algum tratamento imunossupressor