Biliary atresia: a multidisciplinary approach to diagnosis and management.

CONTEXT: Biliary atresia is an inflammatory cholangiopathy of infancy that results in progressive fibrosis and obliteration of bile ducts and represents the main indication for liver transplant in young children. In spite of extensive investigation, its etiology has remained poorly understood. Timely surgical intervention (Kasai procedure) may result in significant benefit to these patients and represents the final goal of an accurate diagnostic evaluation. OBJECTIVE: To present an overview of biliary atresia, including clinical and surgical approaches to this disease, with emphasis on the histopathologic evaluation. DATA SOURCES: Review of relevant literature indexed in PubMed (US National Library of Medicine). CONCLUSION: A well-coordinated multidisciplinary approach is required in the assessment of suspected cases of biliary atresia. Pathologic examination of biopsy specimens is an integral part of the diagnostic algorithm and, therefore, plays a pivotal role in the diagnostic evaluation of this disease.

The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis.

Steatohepatitis and metabolic syndrome are increasingly recognized as important risk factors for development of hepatocellular carcinoma. We have recently described a histologic subtype of hepatocellular carcinoma termed steatohepatitic hepatocellular carcinoma, which shows features resembling steatohepatitis in the nonneoplastic liver. The present study is undertaken to assess the association between the steatohepatitic hepatocellular carcinoma variant and underlying steatohepatitis and features of metabolic syndrome. We examined all hepatocellular carcinomas diagnosed on resections and explant specimens over a 3.5-year period at our institution. Tumors were classified as either conventional hepatocellular carcinoma or steatohepatitic hepatocellular carcinoma variant based on their predominant histopathologic pattern. The underlying chronic liver disease in each case was determined. The steatohepatitic hepatocellular carcinoma variant represented 13.5% (16/118) of cases. All but one case of steatohepatitic hepatocellular carcinoma occurred in patients with underlying steatohepatitis. Steatohepatitic hepatocellular carcinoma was diagnosed in 35.7% of patients with either nonalcoholic steatohepatitis or alcoholic liver disease compared with 1.3% of patient with other chronic liver diseases (P < .0001). The steatohepatitic hepatocellular carcinoma group had a significantly higher number of metabolic syndrome risk factors (2.44 versus 1.48, P = .01) and a higher percentage of patients with at least 3 metabolic syndrome components (50% versus 22.5%, P = .02). Immunohistochemically, there were diffuse loss of cytoplasmic CK8/18 and increased numbers of activated hepatic stellate cells within steatohepatitic hepatocellular carcinoma, in a pattern identical to that seen in steatohepatitis in nonneoplastic liver. Hepatocellular carcinomas showing a "steatohepatitic" histologic phenotype are strongly associated with underlying steatohepatitis and metabolic syndrome. This association further supports a possible role of steatohepatitis in human hepatocarcinogenesis.

Recurrent hepatitis C and acute allograft rejection: clinicopathologic features with emphasis on the differential diagnosis between these entities.

Chronic hepatitis C virus infection is the leading etiology for liver transplantation in the United States. Recurrent hepatitis C occurs nearly universally in these patients and represents a serious posttransplantation complication. Despite the detailed characterization of the histologic features of both recurrent hepatitis C and acute cellular rejection (ACR) over the last decades, the pathologic distinction between these 2 conditions remains one of the greatest diagnostic challenges in liver pathology. An accurate diagnosis, nevertheless, plays an essential role in patient management, as different therapeutic strategies are used for these conditions. In this review, the clinicopathologic features of posttransplantation recurrent hepatitis C and ACR are discussed, with emphasis on distinguishing histopathologic features, morphologic variants, ancillary techniques, and diagnostic pitfalls.

The concept of hepatic artery-bile duct parallelism in the diagnosis of ductopenia in liver biopsy samples.

Absence of bile ducts (BDs) in >50% of portal tracts is currently the most widely accepted criterion for the diagnosis of ductopenia. In this study, we describe an alternative method for the quantitative assessment of BDs based on the percentage of portal tracts containing unpaired hepatic arteries (HAs). Diagnostic criteria for ductopenia were defined as follows: 1. presence of at least 1 unpaired HA in >10% of all portal tracts; 2. at least 2 unpaired HAs present in different portal tracts in a given sample. In liver biopsies from patients with primary biliary cirrhosis and suspected chronic allograft rejection (n = 32), loss of BD was detected in 59.4% of patients using the unpaired HA method compared with 43.7% (P = 0.31), 21.9% (P = 0.005), and 12.5% (P = 0.001) by the traditional method, depending on specific adequacy criteria used (no adequacy criteria, >10 portal tracts, or >5 complete portal tracts per biopsy, respectively). The percentage of portal tracts containing BD(s) was significantly affected by the degree of portal inflammation, fibrosis stage, percentage of complete portal tracts, and biopsy width, whereas none of these factors influenced the prevalence of unpaired arteries. The unpaired HA method showed higher sensitivity for the detection of mild degrees of loss of BD compared with the traditional method, and was not influenced by factors that affected the percentage of portal tracts containing BDs.

Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease.

AIM: To assess the role of IgM and IgG immunohistochemistry (IHC) in the evaluation of autoimmune liver conditions--autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). METHODS: Forty one biopsies from untreated patients diagnosed with autoimmune liver disease (AIH, n = 20; PBC, n = 13; PSC, n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected. IgM and IgG-positive plasma cells were counted in each sample. RESULTS: A predominance of IgG-positive plasma cells was seen in AIH (90% of cases), PSC (75% of cases), and chronic hepatitis C (100% of cases), while IgM-positive plasma cells predominated in PBC (92.8% of cases). The IgM /IgG ratio (< 1 or > or = 1) accurately distinguished PBC from AIH in 90.9% of cases (sensitivity = 92.3%, specificity = 90%), and PBC from either AIH or PSC in 87.8% of cases (sensitivity = 92.3%, specificity = 85.7%). CONCLUSION: Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC, while other forms of liver disease analyzed in this study, including AIH, typically show an IgG-predominant plasma cell infiltrate. Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.

Hepatic stellate cells and liver fibrosis.

Substantial evidence now exists to recognize hepatic stellate cells (HSCs) as the main matrix-producing cells in the process of liver fibrosis. Liver injury of any etiology will ultimately lead to activation of HSCs, which undergo transdifferentiation to fibrogenic myofibroblast-like cells. Quantitative analysis of HSC activation by immunohistochemistry has been shown to be useful in predicting the rate of progression of liver fibrosis in some clinical situations. In the activation process, transforming growth factor beta is thought to be the main mediator of fibrogenesis and platelet-derived growth factor is the major inducer of HSC proliferation. Different platelet-derived growth factor and transforming growth factor beta inhibitors have been shown to effectively prevent liver fibrosis in animal models and represent promising therapeutic agents for humans.

Hepatocellular carcinoma in patients undergoing orthotopic liver transplantation: radiological findings with anatomopathological correlation in Brazil.

BACKGROUND: Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Imaging techniques, specially computed tomography and ultrasound, are among the most useful diagnostic tools, although the accuracy of these methods may have a significant variability. AIMS: To determine the prevalence of hepatocellular carcinoma in cirrhotic patients undergoing orthotopic liver transplantation at "Santa Casa de Misericórdia" of Porto Alegre, RS, Brazil; to estimate the sensitivity of computed tomography and ultrasound in pretransplantation detection of hepatocellular carcinoma in this population; to correlate the radiological characteristics with anatomopathological findings. MATERIALS AND METHODS: Retrospective prevalence study. POPULATION: adult, cirrhotic patients undergoing orthotopic liver transplantation from January 1990 to July 2003. Among the 292 transplanted patients, 31 cases of hepatocellular carcinoma were diagnosed, of which 29 were included in the study. Tumor characteristics in both ultrasound and computed tomography were compared to those observed in anatomopathological examination. RESULTS: Prevalence of hepatitis C virus infection among patients with diagnosis of hepatocellular carcinoma was 93.5%, and the prevalence of hepatocellular carcinoma among transplanted patients was 10.6%. The overall sensitivity of the imaging techniques was 70.3% for computed tomography and 72% for ultrasound. CONCLUSION: The prevalence of hepatocellular carcinoma at our institution, as well as the sensitivity of both ultrasound and computed tomography to detect such tumors at pretransplantation screening were similar to those found by other authors, while the prevalence of hepatitis C virus infection, the most common etiological agent for liver disease in our patients, is one of the highest ever reported in literature. Factors influencing hepatocellular carcinoma detection rates were: time from examination to liver transplantation; acquisition of computed tomography images during arterial phase; lesion size. Arterial phase proved to be the most useful part of computed tomography examination in this study.

Hepatocellular carcinoma in patients undergoing orthotopic liver transplantation: radiological findings with anatomopathological correlation in Brazil

RACIONAL: O carcinoma hepatocelular é um dos tumores malignos mais comuns em todo o mundo. Exames de imagens, especialmente tomografia computadorizada e ultra-sonografia, estão entre as principais técnicas diagnósticas, embora a acurácia destes métodos possa apresentar significativa variabilidade. OBJETIVOS: Determinar a prevalência de carcinoma hepatocelular em pacientes cirróticos submetidos a transplante hepático na Santa Casa de Misericórdia de Porto Alegre, RS; estimar a sensibilidade da tomografia computadorizada e da ultra-sonografia na detecção pré-transplante de carcinoma hepatocelular nesse grupo de pacientes; correlacionar características radiológicas com achados anatomopatológicos. MATERIAIS E MÉTODOS: Estudo de prevalência retrospectivo. População: pacientes adultos, cirróticos, submetidos a transplante hepático de janeiro de 1990 a julho de 2003. Entre os 292 pacientes transplantados, foi diagnosticado 31 casos de carcinoma hepatocelular, dos quais 29 foram incluídos no estudo. As características tomográficas e ecográficas dos tumores diagnosticados pré-transplante foram comparadas com as observadas em exame anatomopatológico. RESULTADOS: A prevalência da infecção pelo vírus da hepatite C nos pacientes com diagnóstico de carcinoma hepatocelular foi de 93,5% e a prevalência deste entre os pacientes transplantados foi de 10,6%. A sensibilidade dos métodos de imagem na detecção de casos de carcinoma hepatocelular foi de 70,3% para tomografia computadorizada e de 72% para ecografia. CONCLUSAO: A prevalência de carcinoma hepatocelular na instituição onde foi desenvolvido o estudo, bem como a sensibilidade da ultra-sonografia e da tomografia computadorizada para detecção dessa neoplasia na avaliação pré-transplante foi semelhante à relatada na literatura. Em contrapartida, a prevalência de infecção pelo vírus da hepatite C, fator etiológico de hepatopatia mais freqüente nos pacientes desta série, é das maiores já relatadas. Os fatores que influenciaram as taxas de detecção de carcinoma hepatocelular foram: tempo decorrido entre realização do exame e transplante; realização de tomografia computadorizada com fase arterial; tamanho da lesão. A fase arterial provou ser a mais importante no diagnóstico de carcinoma hepatocelular neste estudo.

Gliossarcoma de tronco cerebral em paciente pediátrico: relato de caso / Brain stem gliosarcoma in pediatric patient: a case report

Os autores relatam o caso de um paciente branco, de quatro anos de idade, com comprometimento neurológico progressivo. Tomografia computadorizada do crânio e ressonância magnética evidenciaram lesão expansiva no tronco cerebral. Subseqüentemente, foi feito diagnóstico histopatológico de gliossarcoma. Trata-se de um tumor raro do sistema nervoso central que, na grande maioria dos casos, acomete pacientes acima dos 40 anos de idade e tem localização supratentorial. Há poucos casos relatados de gliossarcomas em crianças, sobretudo na região infratentorial. Dados epidemiológicos, assim como achados mais freqüentes na tomografia computadorizada e ressonância magnética, são discutidos.

Alterações morfológicas e funcionais em pacientes com transtorno obsessivo-compulsivo: avaliação por métodos de imagem / Morphological and functional alterations in patients with obsessive-compulsive disorder: evaluation by imaging techniques

A etiopatogenia do transtorno obsessivo-compulsivo é pouco compreendida. Inúmeras evidências indiretas, tais como alterações eletroencefalográficas, neuropsicológicas, bem como presença de sintomas desta doença em pacientes com lesões neurológicas adquiridas, são sugestivas de anormalidades em regiões encefálicas específicas. Com o advento de novas técnicas de imagem, nas últimas décadas, tem sido possível pesquisar a existência de alterações anatômicas e funcionais em diversas estruturas do SNC. A maioria dos estudos na literatura aponta para um provável acometimento de córtex frontal, núcleos da base, vias córtico-estriatais e estruturas límbicas. O significado das anormalidades em cada uma destas regiões, assim como as possíveis interações entre elas, ainda não são bem compreendidas.

Cisto hidático pulmonar gigante: relato de um caso / Giant hydatid lung cyst: a case report

Os autores relatam o caso de um paciente do sexo masculino, com 55 anos de idade, branco, com diagnóstico radiológico e histopatológico pós-cirúrgico de cisto hidático pulmonar gigante. A epidemiologia, fisiopatologia e características radiológicas desta doença são discutidas

The authors report a case of a 55-year-old white male patient with radiological and postsurgical histopathological diagnosis of a giant lung hydatid cyst. The epidemiological, physiopathological and radiological findings of this disease are discussed.

Riscos para a saúde fetal associados com o uso de benzodiazepínicos na gestaçäo: uma revisäo / Fetal hazards associated with use of benzodiazepines during the pregnancy: a review

Os benzodiazepínicos estäo entre os fármacos mais amplamente utilizados pela populaçäo, tanto sob forma de prescriçäo como através da automedicaçäo. Estima-se que cerca de 50 por cento das gestaçöes näo säo planejadas e, entre elas, é comum o uso de tais substâncias. No Sistema Nacional de Informaçäo sobre Agentes Teratogênicos de Porto Alegre (Siat), pertecente ao Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre, foram atendidas 3.107 consultas, sendo que 5,5 por cento se deviam ao uso de benzodiazepínicos. Apesar de os primeiros estudos sobre a teratogenicidade dos benzodiazepínicos em seres humano terem apontado para um aumento significativo na taxa de malformaçöes congênitas, estudos posteriores näo confirmaram este achado. Em relaçäo aos efeitos a longo prazo em crianças expostas intra-útero, näo há evidências, até o momento, de alteraçöes neurocomportamentais nos estudos a longo prazo. Contudo, os benzodiazepínicos, quando usados durante um período prolongado na gravidez, podem afetar adversamente o neonato e, como outras substâncias com açäo sobre o sistema nervoso central, säo potenciais teratógenos. Assim, o seu uso deve ser evitado e restrito somente às raras situaçöes na qual o benefício terapêutico para a mäe sobrepöe o seu potencial risco para o recém-nascido

Fibrose pulmonar grave: achado incomum em lúpus eritematoso sistêmico: relato de um caso / Severe pulmonary fibrosis: an uncommon finding in systemic lupus erythematosus: a case report

Os autores relatam o caso de uma paciente do sexo feminino, 51 anos de idade, branca, com diagnóstico estabelecido de lúpus eritematoso sistêmico associado a evidência radiológica de fibrose pulmonar grave. A epidemiologia das manifestações pleuropulmonares de lúpus eritematoso sistêmco, dando ênfase à fibrose pulmonar, é discutida.