RESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) currently is one oft the most common reasons for chronic liver injury in the western world. In the European and American population the prevalence is up to 30â%. The medical supply of German patients with NAFLD is variable and has not been analyzed to date. METHODS: We sent questionnaires to all university liver centers in Germany (11 questions) concerning the medical supply of patients with NAFLD. Questions included the rate of patients with fatty liver disease in the outpatient clinics, metabolic comorbidities and the kind of assignment. Besides that, individual clinical standards were documented. We compared longitudinal changes between 2008 and 2013. RESULTS: The return rate of questionnaires was 65â% (nâ=â20). Analysis showed that the portion of NAFLD patients in the university outpatient clinics had increased between 2008 and 2013 with the predominant part of patients being assigned from external practitioners and not from internal departments of the hospital. Only few patients were assigned by diabetologists or endocrinologists, but on the other hand most liver outpatient clinics investigated their NAFLD patients for metabolic disorders. Cooperation between liver outpatient clinics and other medical services was moderate and was rated average, joint conferences were held rarely. Follow-up visits of patients with NAFLD take place regularly in all centers, however based on different criterions. A consistent algorithm concerning risk assessment and invasive workup does not exist. CONCLUSION: The awareness concerning patients with NAFLD seems to have grown in recent years. Nevertheless, the medical supply of these patients is quite heterogenous and consistent standards do not exist. Therefore, a common guidline is urgently required.
Assuntos
Gastroenterologia/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pacientes/estatística & dados numéricos , Encaminhamento e Consulta/estatística & dados numéricos , Carga de Trabalho/estatística & dados numéricos , Alemanha/epidemiologia , Pesquisas sobre Atenção à Saúde , Humanos , Prevalência , Revisão da Utilização de Recursos de SaúdeRESUMO
BACKGROUND: Following the introduction of the MELD score, the survival rates have worsened after liver transplantation (LTX) in Germany. Existing organ shortages, shorter survival rates after LTX, and failures in the liver allocation process provide true challenges. Facilitated by a structured questionnaire, the appropriate German liver transplantation actors were approached with regard to these challenges for the first time. The aim was to provide a balanced experts' view in an anonymous fashion thereby identifying areas for potential improvement. METHOD: Data collection was performed by a structured, standardised, anonymous survey of all LTX centres in Germany. RESULTS: We received 75â% replies of the questionnaires, 35 of 36 participants responded to more than 75â% of all questions. The following key points were highlighted. A minimum amount of LTX per centre was deemed important and monetary incentives must not exist. The ultimate goal of LTX is a prolongation of life and social as well as occupational reintegration. Quality management and transparent LTX registers are prerequisites for both adequate organ allocation and distribution of resources in order to achieve the best possible transplant outcomes. CONCLUSION: The German liver transplant experts consider transparency of organ allocation and systematic evaluation of the quality of transplant centres and the transplantation process itself to be mandatory, however, executed in a participatory way. A scoring system to facilitate the decision making process in order to predict the likelihood of satisfactory LTX outcome thereby circumventing some of the ethical and constitutional doubts would be highly appreciated.
Assuntos
Acesso à Informação/legislação & jurisprudência , Hospitais Especializados/legislação & jurisprudência , Falência Hepática/cirurgia , Transplante de Fígado/legislação & jurisprudência , Programas Nacionais de Saúde/legislação & jurisprudência , Complicações Pós-Operatórias/mortalidade , Garantia da Qualidade dos Cuidados de Saúde/legislação & jurisprudência , Alocação de Recursos/legislação & jurisprudência , Alemanha , Humanos , Falência Hepática/mortalidade , Testes de Função Hepática , Transplante de Fígado/mortalidade , Seleção de Pacientes , Inquéritos e Questionários , Análise de Sobrevida , Doadores de Tecidos/legislação & jurisprudência , Doadores de Tecidos/provisão & distribuição , Revelação da Verdade , Listas de Espera/mortalidadeRESUMO
With an incidence of 523â000 new cases a year hepatocellular carcinomas (HCCs) belong to the most frequent cancer entities worldwide. Diagnostic and therapeutic procederes have been improved during the last years. Surveillance of patients with high risk factors leads to an early diagnosis. Up to now the detection of early HCCs represents the best prerequisite for any curative therapy. The present synopsis summarises the current guidelines of the European Association for the Study of the Liver (EASL) and the European Organisation for Research and Treatment of Cancer (EORTC) with a special focus on screening and surveillance of risk groups.
Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/epidemiologia , Quimioembolização Terapêutica , Estudos Transversais , Europa (Continente) , Seguimentos , Hepatectomia , Humanos , Neoplasias Hepáticas/epidemiologia , Guias de Prática Clínica como Assunto , Prognóstico , Fatores de RiscoRESUMO
INTRODUCTION: Non-alcoholic steatohepatitis (NASH) was first described in 1980 and has emerged from an anecdotal disease to a widely distributed liver disease in the current decade. METHODS: This review is based on publications in PubMed and our own experiences and deals with basic pathophysiological aspects, diagnostic, and therapeutic tools as well as with the modern management of this serious liver disease. RESULTS: For a long time the potenial for serious liver destruction and enhanced liver mortality by NASH has been observed. The recognition of the metabolic origin of NASH has contributed to diagnostic as well as therapeutic approaches. Since then patients with metabolic syndrome are often screened for liver disease. NASH might worsen other chronic liver diseases but should be judged as an independent illness rather than the exclusion of other potential liver diseases. Furthermore, non-alcoholic steatohepatitis has systemic consequences concerning insulin resistance, metabolic complications and cardiovascular diseases. PERSPECTIVES: Future research should concentrate on non-invasive screening strategies, identification of risk factors, evaluation of hepatocellular carcinogenesis and new therapeutic targets.
Assuntos
Hepatopatia Gordurosa não Alcoólica/diagnóstico , Causas de Morte , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/mortalidade , Complicações do Diabetes/fisiopatologia , Diagnóstico Diferencial , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/mortalidade , Fígado Gorduroso/fisiopatologia , Fígado Gorduroso/terapia , Humanos , Resistência à Insulina/fisiologia , Fígado/fisiopatologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/mortalidade , Cirrose Hepática/fisiopatologia , Cirrose Hepática/terapia , Programas de Rastreamento , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/mortalidade , Síndrome Metabólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/terapia , Prognóstico , Fatores de RiscoRESUMO
A 75-year-old woman was found to have left-sided pleural effusion and endoscopy revealed the rare entity of adenoid cystic carcinoma metastases in the gastric mucosa. Approximately 20% of patients with this carcinoma suffer from distant metastases. For the initial staging detection of adenoid cystic carcinoma metastasis with positron emission tomography (PET) or PET computed tomography (CT) is recommended. The recurrent t(6;9)(q22-23;p23-24) translocation that results in a fusion of the two transcription factor genes MYB and NFIB is detectable in half of the cases. As in our case molecular pathology can confirm the correct diagnosis and identification of the localization of the primary tumor.
Assuntos
Carcinoma Adenoide Cístico/complicações , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/secundário , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Idoso , Diagnóstico Diferencial , Feminino , HumanosRESUMO
Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.
Assuntos
Gastroenteropatias/epidemiologia , Doença Mista do Tecido Conjuntivo/epidemiologia , Esclerodermia Difusa/epidemiologia , Esclerodermia Limitada/epidemiologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Seguimentos , Gastroenteropatias/diagnóstico , Gastroenteropatias/terapia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/terapia , Prognóstico , Sistema de Registros , Esclerodermia Difusa/diagnóstico , Esclerodermia Difusa/terapia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/terapia , Índice de Gravidade de Doença , Inquéritos e Questionários , Fatores de TempoAssuntos
Gastroenterologia/normas , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/diagnóstico , Obesidade/prevenção & controle , Guias de Prática Clínica como Assunto , Alemanha , Humanos , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicaçõesRESUMO
Matrix Metalloproteinases (MMPs) are a family of Zn (2 +)-dependent endopeptidases that are considered to be the most potent proteases in the turnover of the extracellular matrix (ECM). In addition to their capability for degradating virtually all protein components of the ECM, MMPs regulate a variety of non-matrix substrates such as chemokines, cytokines and growth factors. Therefore MMPs play a central role in a variety of physiological and pathological processes such as angiogenesis, wound healing and inflammatory response including mucosal inflammation associated with inflammatory bowel disease (IBD). Apart from mucosal destruction in IBD, recent studies have identified several new functions of MMPs for the pathophysiology of the healthy and inflamed intestine. This article summarises the main activities of MMPs in IBD with emphasis on their pathophysiological relevance and potential clinical implications based on the expression and regulation patterns of these enzymes.
Assuntos
Doenças Inflamatórias Intestinais/enzimologia , Mucosa Intestinal/metabolismo , Metaloproteinases da Matriz/metabolismo , Modelos Biológicos , Animais , Pesquisa Biomédica/tendências , HumanosRESUMO
Matrix metalloproteinases (MMPs), in particular MMP-2 and MMP-9, are involved in colon cancer progression and metastasis due to their ability to degrade extracellular matrix (ECM) components. In previous studies we described the MMP-9 hemopexin like domain (MMP-9-PEX) as an MMP-9 antagonist. In the present study it was examined whether recombinant MMP-9-PEX has an inhibitory effect on migration and adhesion of colorectal carcinoma cells. Furthermore, we searched for MMP-9 substrate binding sites within the MMP-9-PEX by surface plasmon resonance. Migration of SW620 and LS174 cells was investigated in a modified Boyden chamber assay. In the presence of 0.2 microg/ml MMP-9-PEX migration of SW620 was decreased by 34%, while addition of 0.4 microg/ml diminished migration by 56%. Migration of LS174 cells was not affected by MMP-9-PEX. Adhesion studies were performed on 96-well plates coated with gelatin, collagen type I, and laminin, respectively. In the presence of MMP-9-PEX, adhesion of SW620 cells to these coating substrates was significantly inhibited. Surface plasmon resonance studies revealed binding of collagen type I and IV, elastin, and fibrinogen to proMMP-9 as well as to MMP-9-PEX. However, equilibrium constants (Kd) indicated a higher affinity of proMMP-9 to the matrix proteins. This could indicate that there is more than one binding site for matrix components within the entire proMMP-9 molecule. Since migration and adhesion of metastatic colorectal carcinoma cells were reduced by MMP-9-PEX, this recombinant MMP-9 antagonist might be of therapeutical interest.
Assuntos
Antineoplásicos/farmacologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Hemopexina/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Colágeno Tipo I/metabolismo , Colágeno Tipo IV/metabolismo , Neoplasias Colorretais/enzimologia , Elastina/metabolismo , Fibrinogênio/metabolismo , Gelatina/metabolismo , Hemopexina/genética , Hemopexina/isolamento & purificação , Hemopexina/metabolismo , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/isolamento & purificação , Metaloproteinase 9 da Matriz/farmacologia , Estrutura Terciária de Proteína/genética , Proteínas Recombinantes de Fusão , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Ressonância de Plasmônio de SuperfícieRESUMO
Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotropic factor are a family of cytokines and neuronal differentiation factors which bind to composite plasma membrane receptors sharing the signal transducing subunit gp130. We have shown recently that IL-6 and leukemia inhibitory factor rapidly activate a latent cytoplasmic transcription factor, acute-phase response factor (APRF), by tyrosine phosphorylation, which then binds to IL-6 response elements of various IL-6 target genes. Here we demonstrate that APRF is activated by all cytokines acting through gp130 and is detected in a wide variety of cell types, indicating a central role of this transcription factor in gp130-mediated signaling. APRF activation is also observed in vitro upon addition of IL-6 to cell homogenates. Protein tyrosine kinase inhibitors block both the tyrosine phosphorylation and DNA binding of APRF. The factor was purified to homogeneity from rat liver and shown to consist of a single 87-kDa polypeptide, while two forms (89 and 87 kDa) are isolated from human hepatoma cells. As reported earlier, the binding sequence specificity of APRF is shared by gamma interferon (IFN-gamma) activation factor, which is formed by the Stat91 protein. Partial amino acid sequence obtained from purified rat APRF demonstrated that it is likely to be related to Stat91. In fact, an antiserum raised against the amino-terminal portion of Stat91 cross-reacted with APRF, suggesting the relatedness of APRF and Stat91. Altogether, these data indicate that APRF belongs to a growing family of Stat-related proteins and that IFN-gamma and IL-6 use similar signaling pathways to activate IFN-gamma activation factor and APRF, respectively.
Assuntos
Citocinas/farmacologia , Proteínas de Ligação a DNA/metabolismo , Interleucina-6/farmacologia , Transativadores , Fatores de Transcrição/metabolismo , Tirfostinas , Células 3T3 , Alcaloides/farmacologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Carcinoma Hepatocelular , Catecóis/farmacologia , Linhagem Celular , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/isolamento & purificação , Genisteína , Inibidores do Crescimento/farmacologia , Humanos , Soros Imunes , Interferon gama/farmacologia , Interleucina-11/farmacologia , Isoflavonas/farmacologia , Cinética , Fator Inibidor de Leucemia , Neoplasias Hepáticas , Linfocinas/farmacologia , Camundongos , Dados de Sequência Molecular , Fatores de Crescimento Neural , Proteínas do Tecido Nervoso/farmacologia , Nitrilas/farmacologia , Oligodesoxirribonucleotídeos/síntese química , Oncostatina M , Peptídeos/síntese química , Peptídeos/imunologia , Peptídeos/farmacologia , Inibidores de Proteínas Quinases , Ratos , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT3 , Transdução de Sinais , Esfingosina/farmacologia , Estaurosporina , Células Tumorais CultivadasAssuntos
Adenoma/diagnóstico , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Adenoma/genética , Adenoma/cirurgia , Idoso , Medula Óssea/patologia , Neoplasias do Colo/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/genéticaRESUMO
To define the role of glycosidic conjugation of bile acids in humans, an in vitro model system is desirable. We studied the formation of glycosidic conjugates of bile acids in primary cultures of human hepatocytes, isolated from organ donor liver, and the human hepatoblastoma cell line, HepG2. Cells were incubated with 100 microM bile acids (chenodeoxycholic, CDCA; hyodeoxycholic, HDCA; and isoursodeoxycholic acids, isoUDCA) and 1-2 mM uridine diphosphoglycosides (UDP-glucose, UDP-Glc; UDP-glucuronic acid, UDP-GlcA, and UDP-N-acetylglucosamine, UDP-GlcNAc), and octyl glucoside. Media were analysed by electrospray-/gas chromatography-mass spectrometry and electrospray with collision induced dissociation. Primary cultures of human hepatocytes formed glycosidic bile acid conjugates with UDP-sugars (6alpha-Glc-HDCA, 6alpha-GlcA-HDCA, and 7beta-GlcNAc-isoUDCA) and octyl glucoside as sugar donors (3alpha-Glc-CDCA). HDCA was completely metabolised to either Glc-HDCA, a compound yet not found in vivo, or GlcA-HDCA. No glycosidic bile acid conjugate was found in media from experiments with HepG2. Thus, primary cultures of human hepatocytes, but not HepG2, are suitable in vitro systems for the study of glycosidic bile acid conjugation reactions.