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Henrique Gama,1 Ronniel Albuquerque,1 David Campos Wanderley,1 Marcelo Antônio Pascoal Xavier,1 Fernanda Maria Farage Osório,2 Cláudia Alves Couto,3 Teresa Cristina de Abreu Ferrari,3 Agnaldo S Lima,4 Paulo Henrique Costa Diniz,3 Paula Vieira Teixeira Vidigal1 1Department of Anatomic Pathology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 2Alpha Institute of Gastroenterology, Hospital das Clínicas Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 3Department of Internal Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 4Department of Surgery, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilCorrespondence: Paulo Henrique Costa Diniz, Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Prof Alfredo Balena Av. 190, Belo Horizonte, Minas Gerais, Brazil, 30130100, Email phdiniz@ufmg.brIntroduction: Hepatocellular carcinoma is the most common primary neoplasia of the liver. Microvascular invasion predicts outcome and defines tumor staging. However, its diagnosis is still a challenge. The present study aims to evaluate inter and intraobserver agreement in identifying the presence of microvascular invasion using conventional and immunohistochemistry histology.Methods: Three pathologists performed the analysis of 76 hepatocellular carcinoma explants to characterize the presence of microvascular invasion using the hematoxylin/eosin stain and immunohistochemistry for CD34. The evaluations were made individually, in two distinct moments. Results were analyzed by the Kappa’s coefficient and ROC curves.Results: Our study demonstrated similar agreement for microvascular invasion between hematoxylin/eosin and CD34 methods. However, the intraobserver agreement values for both methods were higher than the interobserver ones. The accuracy of CD34 in relation to hematoxylin/eosin by ROC curves in intraobserver analysis tends to a high specificity, ranging from 82.1 to almost 100%, with sensitivity of 46.9% to 81.1%. In interobserver analysis, CD34 also has a high specificity (84.3% to 85.5%) while its sensitivity is a little shorter (81.2% to 84.3%).Conclusion: Intraobserver higher agreement allows us to suppose that pathologists employed own criteria to evaluate vascular invasion, reinforcing the need of standardization. ROC Curves analysis showed that the CD34 method is more specific than sensitive. Therefore, immunohistochemistry for CD34 should not be used routinely, but it could be useful to help confirming invasion previously seen by conventional histology.Keywords: hepatocellular carcinoma, vascular invasion, immunohistochemistry, interobserver, intraobserver

Background Portal vein thrombosis (PVT) has been described in nearly 50% of patients who underwent oesophagogastric devascularization combined with splenectomy (EGDS), but no previous study has compared its occurrence in surgical and non-surgical groups. This study aimed to investigate PVT in hepatosplenic schistosomiasis (HSS) and its association with EGDS and upper variceal bleeding (UVB). Methods Retrospectively, 104 HSS individuals were enrolled. Following EGDS, the occurrence of PVT, mesenteric vein thrombosis (MVT), hospital admissions and UVB were recorded. Results EGDS was performed in 27 (26%) patients. PVT and MVT were detected in 30 (33%) and 8 (9.8%) patients, respectively. Patients who underwent EGDS were at greater risk of PVT (63% vs 19.7%; odds ratio [OR] 6.12 [95% confidence interval {CI} 2.3 to 16.1], p Conclusions EGDS was not associated with a decreased frequency of UVB when compared with the non-surgical approach but was an independent risk factor for PVT.

Introdução: O câncer colorretal (CCR) é a terceira neoplasia mais comum no mundo e apresenta altas taxas de mortalidade. A pesquisa de sangue oculto nas fezes (PSOF) é um método de rastreamento simples, não invasivo e validado para rastreamento do CCR. Objetivo: Avaliar os diferentes métodos de PSOF, suas taxas de positividade ao longo dos anos e aderência individual ao exame. Metodologia: Trata-se de estudo transversal retrospectivo que avaliou todos os registros de PSOF realizadas em um laboratório de 2005 a 2019. Os pacientes foram agrupados por faixa etária e sexo e a taxa de positividade foi analisada. A PSOF foi feita em duas etapas até 2015: triagem com guáiaco e, se positivo, confirmava-se o resultado com imunoquímico. Desde 2016, todas as PSOF foram realizadas com o imunoquímico. A amostra final foi de 316,287 exames de 136,735 pacientes. Resultados: 68% dos exames foram realizados em mulheres. Homens tiveram mais resultados positivos (p < 0.001). Houve diferença significativa nas taxas de positividade até 2015 e de 2016 a 2019, quando o único método realizado foi o imunoquímico (1.3% vs. 10.0%; p < 0.001). A proporção de resultados positivos aumentou significativamente com a realização de mais de uma amostra e de mais exames ao longo dos anos (p < 0.001). Conclusão: Esse estudo mostra a importância de campanhas de rastreamento de CCR direcionadas aos homens. O método imunoquímico deve ser empregado como padrão devido a sua maior sensibilidade. Indivíduos que realizaram mais amostras e mais exames têm chance aumentada de rastreamento positivo.

Background Upper variceal bleeding (UVB) is a possible complication of portal hypertension secondary to hepatosplenic schistosomiasis (HSS). Propranolol is a non-selective beta-blocker used as secondary prophylaxis for UVB, but no previous studies have addressed carvedilol effects in rebleeding prevention. Methods A retrospective exploratory study of 57 patients with chronic HSS and index UVB treated with endoscopic variceal ligation and propranolol or carvedilol was conducted. The primary outcome was UVB-free time in the first 12 mo after the initial bleeding episode. Results Propranolol was used for secondary UVB prophylaxis in 43 (75.4%) participants (median dose 80 [interquartile range – IQR 60–80] mg/d) and carvedilol in 14 (24.6%) participants (median dose 12.5 [IQR 7.9–25.0] mg/d). During a 12-mo follow-up, rebleeding was observed in 13 (22.8%) patients, 9 (20.9%) of those treated with propranolol and 4 (28.6%) treated with carvedilol (p=0.715). Mean time from the beginning of drug prophylaxis to rebleeding was 6±3 mo and there was no difference between that for propranolol vs carvedilol subgroups. Portal vein thrombosis did not influence the bleeding recurrence in either subgroup. Conclusion Carvedilol may be equally effective as propranolol in preventing secondary UVB in HSS at 12-mo follow-up.

Background. Primary sclerosing cholangitis (PSC) is associated with a broad phenotypic spectrum in different populations from diverse ethnic and racial backgrounds. This study aimed to describe the clinical characteristics and outcomes of PSC in a multicenter cohort of patients from Brazil. Methods. Data from the Brazilian Cholestasis Study Group were retrospectively reviewed to assess demographic information and clinical characteristics of PSC, as well as the outcomes, such as transplantation-free survival. Results. This cohort included 210 patients. After excluding 33 (15.7%) patients with PSC and overlap syndrome of autoimmune hepatitis, 177 (97 males, median age 33 (21–42) years) with clear-cut PSC were eligible for this study. Most of the patients (n = 139, 78.5%) were symptomatic, and 104 (58.7%) had advanced PSC at the time of diagnosis. Concurrent inflammatory bowel disease was observed in 78 (58.6%) of the investigated patients (n = 133), and most of them had ulcerative colitis (n = 61, 78.2%). The 1- and 5-year survival free of liver transplantation or death were 92.3 ± 2.1% and 66.9 ± 4.2%, respectively, and baseline advanced PSC, pruritus, and elevated bilirubin levels were independent risk factors for the composite adverse outcome. Females were significantly older and had lower bilirubin levels than males at baseline, but survival was not associated with sex. Approximately 12.4% (n = 22) of patients with PSC died, and 32.8% (n = 58) underwent liver transplantation at a median follow-up time of 5.3 and 3.2 years. Conclusion. Multiethnic Brazilian PSC patients exhibited a less pronounced male predominance and a lower frequency of inflammatory bowel disease than Caucasians. Adverse outcomes were more frequent, probably due to advanced disease at baseline.

BACKGROUND: Hepatocarcinogenesis is a multistep process that lead to genetic changes in hepatocytes resulting in neoplasia. However, the mechanisms of malignant transformation seem to differ widely. To know carcinogenesis mechanisms is essential to develop new treatment and prevention methods. OBJECTIVE: The aim of this study is to analyze B-Raf protein immunoexpression in explants with hepatocellular carcinoma (HCC) related to hepatitis C (HCV), in adjacent cirrhotic tissue and in normal livers. We also associated the immunoexpression with known HCC related histopathogical prognostic features. METHODS: Livers from 35 patients with HCV related cirrhosis and HCC that underwent liver transplantation or hepatectomy at Clinical Hospital – UFMG and 25 normal livers from necropsy archives were studied. Tumors were classified according to: tumor size, vascular invasion and differentiation grade. B-Raf protein expression was determined by immunohistochemistry. RESULTS: B-Raf was strongly expressed in the HCV cirrhotic parenchyma cytoplasm of 17.1% cases and in 62.9% of HCC samples. Strong B-Raf protein staining was associated with tumor tissue (P

Budd Chiari syndrome (BCS) is an uncommon condition defined as an obstruction in the hepatic venous outflow tract in the absence of cardiac/pericardial disorders as well as hepatic veno-occlusive d...

Context Studies on epidemiology of hepatocellular carcinoma and modalities of therapy used to treat this condition are scarce in Brazil. Our aim was to characterize hepatocellular carcinoma according to etiology of the underlying chronic liver disease, and treatment modalities, in a referral center in Brazil. Methods All cases of hepatocellular carcinoma registered in the Department of Pathology during a 12-year period (1998-2010) were included. Demographic data, etiology of the underlying liver disease and treatment performed were collected. Results This case series included 215 patients, mean age 57.3 (± 14.1) years, 164 (76.2 %) male. Virus C and virus B infection were detected in 88 (43%) and 47 (23%) patients, respectively. Ethanol abuse alone or combined with other etiologies was identified in 64 (32%) individuals. Schistosomiasis was found in 18 (9%) patients. Liver transplantation was the treatment of choice in 112 (51%) patients. This procedure was more frequently performed in hepatitis C virus-related hepatocellular carcinoma (70%) than B virus-related hepatocellular carcinoma (17%). Tumor resection was performed in 40 (18%) individuals, ethanol injection or thermo ablation in 18 (14%), and chemoembolization in 14 (7%). In 40 (19.4%) patients no treatment was performed and this percentage remained constant over the years. Conclusions Chronic hepatitis C, followed by ethanol abuse and chronic hepatitis B were the leading causes of underlying chronic liver disease associated with hepatocellular carcinoma. The results show a trend of increasing incidence of hepatocellular carcinoma; however, the proportion of untreated patients remained constant over the analyzed period. Contexto Estudos sobre epidemiologia do carcinoma hepatocelular e terapias utilizadas em seu tratamento são escassos no Brasil. O objetivo foi caracterizar o carcinoma hepatocelular quanto à etiologia da hepatopatia crônica subjacente e modalidades terapêuticas empregadas, em um centro de referência no Brasil. Método Todos os casos de carcinoma hepatocelular registrados no Departamento de Patologia em período de 12 anos (1998-2010) foram incluídos. Dados demográficos, etiologia da hepatopatia crônica e tipo de tratamento realizado foram coletados dos prontuários. Resultado Esta série de casos incluiu 215 pacientes, com média de idade 57,3 (± 14,1) anos, 164 (76,2%) do sexo masculino. Infecções virais C e B foram detectadas em 88 (43%) e 47 (23%), respectivamente. Abuso de etanol isoladamente ou associado a outras causas foi identificado em 64 (32%) indivíduos. Esquistossomose foi encontrada em 18 (9%) indivíduos. Transplante hepático foi o tratamento de escolha em 112 (51%) pacientes. Esse procedimento foi mais frequentemente realizado em carcinoma hepatocelular relacionado com hepatite C (70%) do que hepatite B (17%). Ressecção cirúrgica foi realizada em 40 (18%) indivíduos, alcoolização ou termo-ablação em 18 (14%) e quimioembolização em 14 (7%). Em 40 (19,4%) pacientes nenhum tratamento foi empregado e esta porcentagem permaneceu constante ao longo dos anos do estudo. Conclusões Hepatite viral C seguida de abuso de etanol e hepatite viral B foram as causas de hepatopatia crônica mais frequentemente associadas ao carcinoma hepatocelular. Os resultados mostram tendência a aumento da incidência do carcinoma hepatocelular; no entanto, a proporção de pacientes não-tratados permaneceu constante ao longo dos anos analisados.

cellular alteration (FCA), hepatocellular adenomas and carcinomas, andmixed hepatocellularcholangiocellular carcinomas. Studies describing these hepatic lesions did not describe the microbial pathogen status of these mice. Because the mouse pathogen Helicobacter hepaticus has been shown to cause hepatitis and liver cancer in susceptible mice and is widespread in researchmouse colonies, it was of interest to determine whether enterohepatic Helicobacter infection was responsible for the lesions seen in this important model of liver cancer. In this study, Helicobacter-free 2 month old FXR knock-out (KO) mice were inoculated with either H. hepaticus or sterile media by oral gavage and evaluated for liver pathology at 1 year post-infection. Infected mice had a 75% incidence of hepatic FCA and 50% incidence of multiple FCA, while such lesions were not noted in sham-dosed FXR KO mice. This correlated with an increase in hepatitis index, which was 4-fold elevated in infected FXR KO mice compared to sham controls. Interestingly, the hepatic FCA incidence noted in H. hepaticus infected mice is similar to that seen in previous FXR KO tumorigenesis studies. These results are consistent with our previous study that described H. hepaticus-associated tumor promotion in constitutive androstane receptor KO mice. Additionally, this study further emphasizes the importance of gastrointestinal flora and laboratory mouse pathogen status in the utilization of experimental models of neoplasia. This study noted hepatic FCA, a pre-neoplastic lesion, and so it remains possible that infection with other Helicobacter species, other gastrointestinal flora changes, or other undefined factors contributed to the tumor development observed in previous reports. Studies are currently underway in our laboratory to characterize the metabolic phenotypes seen in H. hepaticus-infected FXR mice.