RESUMO
BACKGROUND: Histological characterisation of a biliary duct stenosis can be essential for further therapeutic steps. Access to the stenosis is not given in every patient by endoscopic retrograde cholangiography. In these cases, a percutaneous transhepatic cholangiodrainage (PTCD) may be helpful. The optimal preparation and diagnostic precision of taking a biopsy by PTCD is not sufficiently evaluated. METHODS: After a training phase of 10 patients, PTCDs in 30 patients with a biliary duct stenosis and lack of adequate drainage by ERC were done in a time range of 24 months. The stenosis was passed with a wire and then a directed forceps-biopsy was performed in a "cross and push" technique (Transluminal Biliary Biopsy Forceps Set, Cook Medical™), using a wire-guided introducer (7 Fr. inner diameter). The result of the histological survey was then correlated with the definite diagnosis. The follow-up time was 18 months. RESULT: Out of 30 patients, there were 22 (73â%) with a malignant stenosis (10 biliary duct neoplasms, 12 non-biliary carcinoma/metastases/lymphomas). Eight (27â%) out of 30 patients had a benign stenosis. In case of all 30 patients, there was enough tissue gained by biopsy for histologic survey. Sub-group analysis was performed for biliary duct cancer and non-biliary cancer. Thereby, 8 out of 10 patients with biliary duct neoplasms were also classified as malignant by histology (sensitivity 80â%); whereas, only 8 out of 12 non-biliary cancers could be histologically classified as malignant (sensitivity 66.6â%, difference not significant, pâ=â0.0577). In all patients with benign stenosis, histological evaluation of biopsies revealed benign histology (specificity 100â%). There were no intervention-related complications. CONCLUSION: This prospective cohort-study shows a high diagnostic precision for the percutaneous transductal biopsy-set to evaluate an undetermined biliary duct stenosis-particularly in biliary processes. Because it can be difficult to gain histology in malignant biliary duct processes using different methods, the "cross and push" biopsy completes the spectrum of diagnostic procedures.
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Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Biópsia/métodos , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Constrição Patológica , Drenagem , Humanos , Projetos Piloto , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
Treatment of adenoma of the major duodenal papilla is often a challenge for the endoscopist. We report about two patients with papillary adenoma who had residual adenoma in the center of the ductus hepatocholedochus papillary region after endoscopic papillectomy. Due to missing possibility of further endoscopic resection we carried out endobiliary radiofrequency ablation instead of surgical treatment. In follow-up examination, there where no macroscopic or histological relapse, therefore endobiliary radiofrequency ablation needs to be discussed as an alternative to surgical therapy option.
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Adenoma/cirurgia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Adenoma/patologia , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Endoscopia Gastrointestinal , Humanos , Recidiva Local de Neoplasia , Ablação por Radiofrequência , Resultado do TratamentoRESUMO
The endoscopic full-thickness resection (EFTR) is established in ablation of recurrent colorectal adenomas, which cannot be removed by endoscopic resection in cases of fibrosis. The EFTR can be applied with low risk, in one step, with the use of special devices, such as the full-thickness resection device (FTRD®). The main risks described in literature are bleeding and perforations. The mentioned perforations were explained by previous defects of the device system or patient-related predisposed parameters for perforation.We report the case of a 55-year old woman who underwent an endoscopic full-thickness resection with the FTRD® due to a recurrent adenoma with high-grade intraepithelial neoplasm in the sigmoid. After primary uncomplicated development, she presented with a secondary perforation with purulent peritonitis seven days after intervention, so a sigmoid-resection was necessary. There were no signs of defects with the FTRD® system or patient-related predisposed parameters, which prefer a perforation.Our case-report demonstrates the necessity for clinical follow up, after primary uncomplicated endoscopic full-thickness resection, to recognize delayed complications.
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Adenoma , Colectomia , Colo Sigmoide , Neoplasias Colorretais , Perfuração Intestinal , Complicações Pós-Operatórias , Sigmoidoscopia , Adenoma/cirurgia , Colectomia/efeitos adversos , Colo Sigmoide/lesões , Neoplasias Colorretais/cirurgia , Endoscopia , Feminino , Humanos , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/etiologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Sigmoidoscopia/efeitos adversos , Resultado do TratamentoRESUMO
We report the case of a 53-year-old female patient who was transplanted with the liver of a 71-year-old male donor for advanced primary sclerosing cholangitis (PSC) and who additionally was diagnosed with a histologically non-classifiable colitis shortly before transplantation. Upon follow-up abdominal ultrasound 4 months after transplantation, a liver lesion measuring 16â×â23âmm was detected in the transplanted liver. This lesion had not been noticed immediately after transplantation and showed a pattern suspicious for malignancy in contrast-enhanced ultrasound. In line, a biopsy revealed the presence of a metastasis of an adenocarcinoma of colorectal origin, suggesting that a colitis- and PSC-associated colorectal cancer of the recipient might have been overseen upon the initial diagnostic workup.âDespite two negative follow-up colonoscopies, this hypothesis was further supported by a strong positive signal in projection to the cecum in a subsequently performed PET/CT-scan. However, surgical resection of the right colon that was performed simultaneously with the atypical resection of the liver metastasis only revealed an inflamed diverticulum but no malignancy in the resected colon segment. Moreover, cytogenetic and molecular genetic testing on the resected specimens clearly attributed the metastasis to the male donor. On the one hand, this case underlines the necessity of endoscopic surveillance of patients with PSC and/or inflammatory bowel disease as well as the challenges in diagnosis of colitis-associated cancer. On the other hand, it shows that the acceptance of organs from elderly donors in times of organ shortage might be linked to an increased risk of donor transmitted malignancies.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Transplante de Fígado/efeitos adversos , Equipe de Assistência ao Paciente/organização & administração , Adenocarcinoma/etiologia , Idoso , Diagnóstico Diferencial , Seleção do Doador/métodos , Feminino , Alemanha , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Doadores de TecidosRESUMO
AIM: To evaluate whether contrast enhanced ultrasound (CEUS) might also be used for response prediction and early response evaluation in patients receiving bevacizumab based chemotherapy for metastasized colorectal cancer. METHODS: Thirty consecutive patients with non primary resectable liver metastases from colorectal cancer underwent CEUS before treatment (CEUS date 1) and before the second (CEUS date 2) and fourth (CEUS date 3) cycle of bevacizumab based chemotherapy. Three parameters [PEAK, Time to peak (TTP) and RISE RATE]were correlated with radiological response. RESULTS: For neoadjuvant purpose a reduction of tumour mass was required to assume clinical response. Based on these response criteria there was a significant (P < 0.001) correlation in TTP between metastases of responders (9.08 s) and non-responders (14.76 s) archived on CEUS date 1. By calculating a standardized quotient (metastases divided by normal liver tissue) we were able to define a cut off, predicting response with a sensitivity of 92.3 % and a specificity of 100 %. To reflect a palliative intention only those patients with progressive disease were classified as non-responders. In this stetting TTP was also significantly (P < 0.01) different between responders and non-responders. In contrast, Peak and Rise rate did not show any significant difference between responder and non-responder. CONCLUSION: CEUS might serve as a surrogate marker to predict treatment response in patients with metastasized colorectal cancer who receive antiangiogenic therapy.
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Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais , Neoplasias Hepáticas , Metástase Neoplásica , Idoso , Bevacizumab , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Meios de Contraste/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologia , UltrassonografiaRESUMO
BACKGROUND: Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for the differentiation between neoplastic and non-neoplastic colorectal polyps. OBJECTIVE: To develop a computer-based method for classification of colorectal polyps. DESIGN: A prospective study. SETTING: University hospital. PATIENTS: A total of 214 patients with colorectal polyps who underwent a zoom NBI colonoscopy. INTERVENTIONS: A total of 434 detected polyps 10 mm or smaller were imaged and subsequently removed for histological analysis. MAIN OUTCOME MEASUREMENTS: Diagnostic performance in polyp classification by 2 experts, 2 nonexperts, and a computer-based algorithm. RESULTS: The expert group and the computer-based algorithm achieved a comparable diagnostic performance (expert group: 93.4% sensitivity, 91.8% specificity, and 92.7% accuracy; computer-based algorithm: 95.0% sensitivity, 90.3% specificity, and 93.1% accuracy) and were both significantly superior to the nonexpert group (86.0% sensitivity, 87.8% specificity, and 86.8% accuracy) in terms of sensitivity, negative predictive value, and accuracy. Subgroup analysis of 255 polyps 5 mm or smaller revealed comparable results without significant differences in the overall analysis of all polyps. LIMITATIONS: No fully automatic classification system. CONCLUSIONS: The study demonstrates that computer-based classification of colon polyps can be achieved with high diagnostic performance.
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Algoritmos , Pólipos do Colo/classificação , Colonoscopia/métodos , Processamento Eletrônico de Dados/métodos , Aumento da Imagem/instrumentação , Óptica e Fotônica , Pólipos do Colo/diagnóstico , Diagnóstico Diferencial , Seguimentos , Humanos , Programas de Rastreamento/métodos , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: Chemotherapeutic options for patients with metastasised colorectal cancer and impaired liver function are limited. Although oxaliplatin and 5-FU are well tolerated as single therapeutic agents, data supporting their use as combination chemotherapy in the setting of severe hepatic dysfunction are insufficient. PATIENTS AND METHODS: Here, we report on 2 patients with colorectal cancer and severe liver dysfunction secondary to hepatic metastases. On admission both patients displayed a bilirubin of > 22 mg/dL and an alkaline phosphatase (AP) of > 350 U/L as signs of extensive hepatic tumor spread. We initiated a 5-FU/oxaliplatin-based combination chemotherapy in both patients. RESULTS: Liver function and clinical performance improved dramatically within the first cycles of therapy in both patients. On radiologic evaluation, we observed 1 partial response and one long-term (10 months) disease stabilization. The toxicity was acceptable in both patients. CONCLUSION: We concluded that oxaliplatin-based combination chemotherapies (eg FOLFOX4) may achieve good tumor response without significant side effects in patients with metastatic colorectal cancer and hepatic dysfunction.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Bilirrubina , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano , Leucovorina/uso terapêutico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , OxaliplatinaRESUMO
PURPOSE: The development of stenosis is a typical complication of Crohn's disease and represents a serious diagnostic and therapeutic challenge. The aim of the present study was to define objective quantitative measures of stricture characteristics (fibrostenotic/cicartricial vs. inflammatory) using contrast-enhanced ultrasound (CEUS) in patients with stenotic Crohn's disease. MATERIALS AND METHODS: During a period of 18 months, 18 consecutive patients with Crohn's disease and manifestation of a localized significant small bowel stenosis were prospectively recruited. Standardized ultrasound (US) examination, color-coded duplex sonography and CEUS using SonoVue® were performed. Quantitative measurements of bowel wall vascularity were determined using computerized algorithms (Bracco QONTRAST software). The quality of stenosis (fibrostenotic vs. inflammatory) was classified in a 4-point scale, and the diagnostic/prognostic power of the US and clinical tests upon initial presentation were compared. RESULTS: We established a novel standardized CEUS procedure using computerized algorithms to quantitatively examine stenoses in Crohn's disease. An inflammatory origin of stenosis correlated significantly with a high Crohn's Disease Activity Index (CDAI) (p < 0.01), the length of stenosis (p < 0.01) as well as the Limberg score (p < 0.01). There was no correlation between the type of stenosis and quantitative results of CEUS. CONCLUSION: Although bowel wall vascularity can be quantitatively assessed in stenotic areas by CEUS, this analysis does not improve the diagnostic power for the objective determination of the quality of stenosis at a single measurement. Semiquantitative analysis of bowel wall vascularity, length of stenosis, and CDAI may help to discriminate the origin of small bowel stenosis in Crohn's disease.
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Doença de Crohn/diagnóstico por imagem , Obstrução Intestinal/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Algoritmos , Meios de Contraste , Doença de Crohn/complicações , Estudos Transversais , Feminino , Fibrose/diagnóstico por imagem , Humanos , Obstrução Intestinal/etiologia , Intestino Delgado/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Monocyte-derived macrophages critically perpetuate inflammatory responses after liver injury as a prerequisite for organ fibrosis. Experimental murine models identified an essential role for the CCR2-dependent infiltration of classical Gr1/Ly6C(+) monocytes in hepatic fibrosis. Moreover, the monocyte-related chemokine receptors CCR1 and CCR5 were recently recognized as important fibrosis modulators in mice. In humans, monocytes consist of classical CD14(+)CD16(-) and non-classical CD14(+)CD16(+) cells. We aimed at investigating the relevance of monocyte subpopulations for human liver fibrosis, and hypothesized that 'non-classical' monocytes critically exert inflammatory as well as profibrogenic functions in patients during liver disease progression. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed circulating monocyte subsets from freshly drawn blood samples of 226 patients with chronic liver disease (CLD) and 184 healthy controls by FACS analysis. Circulating monocytes were significantly expanded in CLD-patients compared to controls with a marked increase of the non-classical CD14(+)CD16(+) subset that showed an activated phenotype in patients and correlated with proinflammatory cytokines and clinical progression. Correspondingly, CD14(+)CD16(+) macrophages massively accumulated in fibrotic/cirrhotic livers, as evidenced by immunofluorescence and FACS. Ligands of monocyte-related chemokine receptors CCR2, CCR1 and CCR5 were expressed at higher levels in fibrotic and cirrhotic livers, while CCL3 and CCL4 were also systemically elevated in CLD-patients. Isolated monocyte/macrophage subpopulations were functionally characterized regarding cytokine/chemokine expression and interactions with primary human hepatic stellate cells (HSC) in vitro. CD14(+)CD16(+) monocytes released abundant proinflammatory cytokines. Furthermore, CD14(+)CD16(+), but not CD14(+)CD16(-) monocytes could directly activate collagen-producing HSC. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the expansion of CD14(+)CD16(+) monocytes in the circulation and liver of CLD-patients upon disease progression and suggest their functional contribution to the perpetuation of intrahepatic inflammation and profibrogenic HSC activation in liver cirrhosis. The modulation of monocyte-subset recruitment into the liver via chemokines/chemokine receptors and their subsequent differentiation may represent promising approaches for therapeutic interventions in human liver fibrosis.
Assuntos
Inflamação/imunologia , Receptores de Lipopolissacarídeos/imunologia , Cirrose Hepática/imunologia , Monócitos/imunologia , Receptores de IgG/imunologia , Estudos de Casos e Controles , Progressão da Doença , Citometria de Fluxo , HumanosRESUMO
BACKGROUND: The frequency of diagnosis of celiac disease has increased since the introduction of serologic testing. The number of patients in whom extraintestinal symptoms reflect the initial manifestation is rising. Common symptoms are changes in blood counts, which can arise from changes in all cell lineages. Among these, iron deficiency anemia is very common, but also thrombocytosis and thrombocytopenia have been reported to manifest themselves within the framework of celiac disease. CASE REPORT: The authors report on a patient with malnutrition, macrocytic anemia, and pronounced thrombocytopenia. Based on changes of peripheral blood smear and endoscopic result, celiac disease was suspected that could be confirmed by histology of duodenal biopsies. The thrombocytopenia was reversible after initiation of gluten-free diet and folic acid substitution. In addition, clinical symptoms resolved and hematologic reconstitution could be observed. CONCLUSION: Similar deficiencies have almost exclusively been observed in patients with increased folic acid requirements during pregnancy or intensive care. Celiac disease must be taken into consideration, if changes in blood counts occur associated with gastrointestinal symptoms.
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Anemia Macrocítica/etiologia , Doença Celíaca/diagnóstico , Trombocitopenia/etiologia , Anemia Macrocítica/diagnóstico , Biópsia , Doença Celíaca/dietoterapia , Doença Celíaca/patologia , Dieta Livre de Glúten , Feminino , Ácido Fólico/administração & dosagem , Humanos , Mucosa Intestinal/patologia , Pessoa de Meia-Idade , Desnutrição Proteico-Calórica/dietoterapia , Desnutrição Proteico-Calórica/etiologia , Desnutrição Proteico-Calórica/patologia , Trombocitopenia/diagnósticoRESUMO
BACKGROUND: Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa. METHODS: fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies. RESULTS: fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c. CONCLUSIONS: Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.
Assuntos
Doença Celíaca/genética , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Chaperonas Moleculares/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doença Celíaca/metabolismo , Linhagem Celular , Criança , Sistema Cromafim/metabolismo , Enterócitos/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Fases de Leitura Aberta , RNA Mensageiro/análise , Valores de Referência , Adulto JovemRESUMO
Hepatocyte transplantation (HT) is still restricted by the limited amount of transplantable cells. Therefore, a better understanding of the mechanisms involved in cellular engraftment, proliferation, and in vivo selection is important. Here we aimed to evaluate the role of the interleukin 6 (IL-6)/glycoprotein 130 (gp130) system for liver repopulation. Mice carrying a conditional hepatocyte-specific deletion of the common IL-6 signal transducer gp130 (gp130(Deltahepa)) were used for HT. First, we compared bone marrow transplantation (BMT), partial hepatectomy (PH), and retrorsine treatment of recipient mice to optimize the in vivo selection of transplanted hepatocytes. BMT combined with PH was sufficient to induce a 30-fold increase in the number of transplanted donor hepatocytes, whereas additional retrorsine pretreatment led to an up to 40-fold increase. Next, the influence of gp130 signaling in hepatocytes on cell selection was evaluated. Wild-type (WT) hepatocytes repopulated WT recipients at the same rate as gp130(Deltahepa) cells. In contrast, liver repopulation by transplanted cells was enhanced in gp130(Deltahepa) recipient mice. This was associated with higher proliferation of donor hepatocytes and enhanced apoptosis in gp130(Deltahepa) recipient livers. Additionally, the acute phase response was strongly induced after HT in WT recipients but blunted in gp130(Deltahepa) recipients. As a result, significantly more liver remodeling, evidenced by stronger hepatic stellate cell activation and collagen accumulation, was found in gp130(Deltahepa) mice after HT. In conclusion, the HT model established here can be efficiently applied to investigate cell-specific mechanisms in liver repopulation. Moreover, we have shown that gp130-dependent pathways in host hepatocytes are important for controlling liver repopulation.
Assuntos
Receptor gp130 de Citocina/metabolismo , Hepatócitos/transplante , Fígado/metabolismo , Reação de Fase Aguda/metabolismo , Animais , Colágeno/metabolismo , Células Estreladas do Fígado/fisiologia , Humanos , Camundongos , Camundongos Transgênicos , Transdução de SinaisAssuntos
Benserazida/administração & dosagem , Catecolaminas/sangue , Levodopa/administração & dosagem , Síndrome das Pernas Inquietas/tratamento farmacológico , Adulto , Antiparkinsonianos/administração & dosagem , Catecolaminas/urina , Diagnóstico Diferencial , Combinação de Medicamentos , Reações Falso-Positivas , Feminino , Humanos , Hipertensão/sangue , Hipertensão/induzido quimicamente , Hipertensão/diagnóstico , Hipertensão/urina , Síndrome das Pernas Inquietas/sangue , Síndrome das Pernas Inquietas/urinaRESUMO
The pathophysiological mechanisms for ileocecal intussusception in children with adenovirus infection are not well characterized. Here we demonstrate coincidence of adenovirus infection and inflammatory neuropathy of myenteric plexus in two children with ileocecal intussusception. Inflammatory neuropathy, an unspecific morphological feature which is found in peristalsis disorders, was morphologically characterized by the influx of CD3 positive lymphocytes in nervous plexus. To our knowledge, this is the first report suggesting peristalsis disorders from inflammatory neuropathy as additional mechanism in the pathophysiological concept of adenovirus-associated ileocecal intussusception.
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BACKGROUND: Critical illness in cirrhotic patients is associated with a poor prognosis and increased susceptibility to infections. Monocyte HLA-DR expression is decreased in cirrhotic patients, but its prognostic value has not been investigated prospectively. METHODS: Thirty-eight critically ill patients with decompensated liver cirrhosis were included in this prospective study. On admission to the intensive care unit (ICU), inflammatory parameters (C-reactive protein, procalcitonin and lipopolysaccharide-binding protein), interleukin (IL)-10, interferon (IFN)-gamma serum levels, tumour necrosis factor (TNF)-alpha ex vivo stimulation (whole blood assay) and HLA-DR expression on monocytes (FACS analysis) were determined. Immune parameters were furthermore measured every third day until discharge from the ICU or death of the patients. RESULTS: Intensive care unit mortality of the cirrhotic patients was 34.2%. During admission, TNF ex vivo, IFN-gamma and HLA-DR expression were lower in non-survivors (all P<0.05), while IL-10 levels were increased in non-survivors compared with survivors (P=0.001). However, individual values clearly overlapped between groups. Prospective analysis revealed that monocyte HLA-DR expression remained stable or increased in survivors, but decreased in non-survivors (P=0.002). A decrease in HLA-DR expression between admission and day 3 was strongly associated with decreased IFN-gamma levels and increased ICU mortality (hazard ratio 3.36, P=0.008), mostly owing to late sepsis. This association was independent of the sequential organ failure assessment and model for end-stage liver disease score. CONCLUSIONS: Here we establish the relative HLA-DR expression (admission/day 3) as a prognostic marker for ICU mortality in critically ill cirrhotic patients. These results may guide the evaluation of immune-modulating therapies in these patients.
Assuntos
Antígenos HLA-DR/metabolismo , Cirrose Hepática/sangue , Monócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-6/sangue , Cirrose Hepática/mortalidade , Falência Hepática/sangue , Falência Hepática/etiologia , Falência Hepática/mortalidade , Falência Hepática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
OBJECTIVE: Enlarged perihilar lymph nodes have been described in patients with primary sclerosing cholangitis (PSC). The aim of the study was to determine the clinical relevance of perihilar lymph nodes in PSC patients with and without cholangiocellular carcinoma (CCC). MATERIAL AND METHODS: The status of perihilar lymph nodes was investigated in 117 patients with PSC using "high-end" ultrasound. Thirty-five of the 117 PSC patients had histologically proven CCC. Lymph node status was correlated with the presence of CCC and inflammatory bowel disease (IBD). RESULTS: Seventy-three percent of PSC patients without CCC and 86% of patients with CCC had enlarged perihilar lymph nodes (NS). In CCC patients, the width of lymph nodes was significantly larger (12+/-6 mm versus 8+/-4 mm; p=0.0001), and the length:width ratio (2.15+/-0.7:1 versus 2.5+/-0.6:1; p=0.004) of the lymph nodes was significantly lower. Thirty-seven percent of PSC patients without CCC and 57% of patients with PSC and CCC had multiple perihilar lymph nodes (p=0.04). In all patients, the presence versus absence of IBD had no influence on the number (84% versus 74%,) and size of perihilar lymph nodes (length: 21+/-10 mm versus 19+/-7 mm). Lymph node status did not correlate with the number of episodes of cholangitis. CONCLUSIONS: Enlarged perihilar lymph nodes are characteristic of patients with PSC. Since perihilar lymph nodes are not predictive of the presence of complicating CCC, such patients should not be excluded from liver transplantation.
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Neoplasias dos Ductos Biliares/complicações , Colangiocarcinoma/complicações , Colangite Esclerosante/complicações , Adulto , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/patologia , Colangite Esclerosante/diagnóstico por imagem , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Linfonodos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
Primary sclerosing cholangitis (PSC) is an important liver disease with major morbidity and mortality. The diagnosis of PSC is confirmed by magnetic resonance cholangiopancreaticography, and endoscopic retrograde cholangiopancreaticography is performed in patients needing therapeutic endoscopy. As a result of the unknown cause of the disease, current medical therapies are unsatisfactory. Nevertheless, high-dose ursodeoxycholic acid should be recommended for treatment of PSC patients because there is a trend toward increased survival. Dominant bile duct stenoses should be treated endoscopically. However, liver transplantation continues to be the only therapeutic option for patients with advanced disease. Estimation of prognosis and timing of liver transplantation should be determined individually for each PSC patient on the basis of all results. The diagnosis and treatment of cholangiocarcinoma (CC) still remain a challenge in PSC patients. Early diagnosis of CC certainly is a prerequisite for successful treatment with surgical resection or innovative strategies such as neoadjuvant radiochemotherapy with subsequent orthotopic liver transplantation. Therefore, endoscopic techniques such as cholangioscopy and/or intraductal ultrasound may be useful diagnostic tools in patients with stenoses suspicious for malignancy.
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Colangite Esclerosante/diagnóstico , Colangite Esclerosante/terapia , Transplante de Fígado/métodos , Algoritmos , Doenças dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Colangite Esclerosante/epidemiologia , Constrição Patológica/terapia , Endoscopia/métodos , Gastroenterologia/métodos , Humanos , Prognóstico , Resultado do Tratamento , Ultrassonografia/métodos , Ácido Ursodesoxicólico/uso terapêuticoRESUMO
BACKGROUND AND AIMS: The constant renewal of enterocytes along the crypt-villus axis (CVA) of human small intestine is due to cell-inherent changes resulting in the apoptotic cell death of senescent enterocytes. The aim of the present study was to examine underlying molecular mechanisms of the cell death at the villus tip. METHODS: Characterization of human acyl-coenzyme A (CoA) synthetase 5 (ACSL5) was performed by cloning, recombinant protein expression, biochemical approaches, and several functional and in situ analyses. RESULTS: Our data show that different amounts of acyl-CoA synthetase 5-full length (ACSL5-fl) and a so far unknown splice variant lacking exon 20 (ACSL5-Delta 20) are found in human enterocytes. In contrast with the splice variant ACSL5-Delta 20, recombinant and purified ACSL5-fl protein is active at a highly alkaline pH. Over expression of ACSL5-fl protein is associated with a decrease of the anti-apoptotic FLIP protein in a ceramide-dependent manner and an increased cell-surface expression of the death receptor TRAIL-R1. Expression analyses revealed that the ACSL5-fl/ACSL5-Delta 20 ratio increases along the CVA, thereby sensitizing ACSL5-fl-dominated cells at the villus tip to the death ligand TRAIL, which is corroborated by functional studies with human small intestinal mucosal samples and an immortalized human small intestinal cell line. CONCLUSIONS: Our results suggest an ACSL5-dependent regulatory mechanism that contributes to the cellular renewal along the CVA in human small intestine. Deregulation of the ACSL5-fl/ACSL5-Delta 20 homeostasis in the maturation and shedding of cells along the CVA might also be of relevance for the development of intestinal neoplasia.
Assuntos
Processamento Alternativo , Apoptose/genética , Coenzima A Ligases/metabolismo , Duodeno/enzimologia , Enterócitos/enzimologia , Regulação Enzimológica da Expressão Gênica , Íleo/enzimologia , RNA Mensageiro/metabolismo , Idoso , Sequência de Aminoácidos , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Células CACO-2 , Caspase 3/metabolismo , Doença Celíaca/enzimologia , Doença Celíaca/genética , Doença Celíaca/patologia , Ceramidas/biossíntese , Coenzima A Ligases/genética , Duodeno/patologia , Retículo Endoplasmático/enzimologia , Enterócitos/patologia , Ativação Enzimática , Humanos , Concentração de Íons de Hidrogênio , Íleo/patologia , Microvilosidades/enzimologia , Microvilosidades/patologia , Pessoa de Meia-Idade , Mitocôndrias/enzimologia , Dados de Sequência Molecular , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Receptores do Fator de Necrose Tumoral/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , TransfecçãoRESUMO
OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with varying severity and progression. This study describes the natural history of PSC patients and evaluates the prognostic significance of clinical, biochemical, and cholangiographic findings constructing a novel prognostic model. METHODS: A population of 273 German PSC patients was studied with a median follow-up time of 76 months (range 1-280 months). Survival curves were analyzed by the Kaplan-Meier method, and prognostic significance of clinical, biochemical, and cholangiographic features recorded at the time of diagnosis was evaluated by multivariate analysis using Cox proportional-hazards regression models. RESULTS: The estimated median survival from the time of diagnosis to death or time of liver transplantation was 9.6 yr. One hundred eight (39.6%) patients underwent liver transplantation. Hepatobiliary malignancies were found in 39 (14.3%) patients of the entire PSC population. Age, low albumin, persistent bilirubin elevation longer than 3 months, hepatomegaly, splenomegaly, dominant bile duct stenosis, and intra- and extrahepatic ductal changes at the time of diagnosis were found to be independent risk factors correlating with poor prognosis and were used to construct a new prognostic model. CONCLUSIONS: A persistent bilirubin elevation for longer than 3 months from the time of diagnosis could be identified as a novel marker correlating with a poor outcome. A new prognostic model was developed to predict progression of PSC, which may be useful in timing of liver transplantation.