RESUMO
Airway epithelium alterations, including squamous cell metaplasia, characterize smokers with and without chronic obstructive pulmonary disease (COPD). The p21 regulates cell apoptosis and differentiation and its role in COPD is largely unknown. Molecules regulating apoptosis (cytoplasmic p21, caspase-3), cell cycle (nuclear p21), proliferation (Ki67/PCNA), and metaplasia (survivin) in central airways from smokers (S), smokers-COPD (s-COPD) and non-smokers (Controls) were studied. The role of cigarette smoke extracts (CSE) in p21, survivin, apoptosis (caspase-3 and annexin-V binding) and proliferation was assessed in a bronchial epithelial cell line (16HBE). Immunohistochemistry, image analysis in surgical samples and flow-cytometry and carboxyfluorescein succinimidyl ester proliferative assay in 16HBE with/without CSE were applied. Cytoplasmic and nuclear p21, survivin, and Ki67 expression significantly increased in large airway epithelium in S and in s-COPD in comparison to Controls. Caspase-3 was similar in all the studied groups. p21 correlated with epithelial metaplasia, PCNA, and Ki67 expression. CSE increased cytoplasmic p21 and survivin expression but not apoptosis and inhibited the cell proliferation in 16HBE. In large airway epithelium of smokers with and without COPD, the cytoplasmic p21 inhibits cell apoptosis, promotes cell proliferation and correlates with squamous cell metaplasia thus representing a potential pre-oncogenic hallmark.
Assuntos
Brônquios/fisiopatologia , Inibidor de Quinase Dependente de Ciclina p21/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar/fisiopatologia , Idoso , Brônquios/enzimologia , Brônquios/metabolismo , Estudos de Casos e Controles , Caspase 3/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Epitélio/fisiopatologia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno Nuclear de Célula em Proliferação/metabolismo , Doença Pulmonar Obstrutiva Crônica/enzimologia , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
AIM: To define the prevalence of different multidetector-row computed tomography (MDCT) vascular patterns and their histopathological correlation with liver explants, and to evaluate the accuracy of MDCT for the diagnosis of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed 125 cirrhotic patients imaged by MDCT before liver transplantation. Three main vascular patterns were identified: hypervascular lesion with washout (Hyper-L-Wo), hypervascular lesion without washout (Hyper-L) and non-hypervascular lesion (Hypo-L). Radiological findings were matched with histopathology of explants. RESULTS: Positive predictive value (PPV) and likelihood ratio (LR) were 95% and 18.66, respectively, for Hyper-L-Wo; 45% and 0.82 for Hyper-L; and 75% and 3 for Hypo-L of 20 mm or larger. Overall accuracy of MDCT for detection and characterisation of HCC was 89% and 43%, respectively. Sensitivity of MDCT for detection and characterisation was related to the lesion size, ranging from 78% (lesion smaller than 10 mm) to 98% (larger than 20 mm) and from 9% to 64%, respectively. MDCT established the accurate stage of disease in 46% of the patients, underestimated in 52% and overestimated in 2%. CONCLUSION: In cirrhotic patients, any Hyper-L-Wo detected by MDCT can be confidently considered to be HCC. Hyper-L larger than 10 mm and Hypo-L of 20 mm or larger are at high risk of HCC. However, even using MDCT and the newest imaging protocols, imaging underestimated the diagnosis of small HCC.
Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/epidemiologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/epidemiologia , Transplante de Fígado/diagnóstico por imagem , Transplante de Fígado/estatística & dados numéricos , Adulto , Idoso , Comorbidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Adulto JovemRESUMO
A wide spectrum of common and uncommon diffuse liver diseases affecting neonatal and pediatric liver transplant candidates is presented and analyzed using 16 and 64 multi-detector row helical CT (MDCT) and 1.5 T MRI fast imaging. Correlation of imaging findings and explanted liver or histology is illustrated in representative cases. Associated uncommon congenital anomalies are shown. In conclusion, in pediatric liver transplant candidates, 16-MDCT and 1.5 T fast MRI are useful for diagnosis and staging of liver disease, as well as for the evaluation of associated congenital anomalies.
Assuntos
Hepatopatias/diagnóstico , Transplante de Fígado , Imageamento por Ressonância Magnética , Tomografia Computadorizada Espiral , Ultrassonografia , Criança , Humanos , Recém-Nascido , Cuidados Pré-OperatóriosRESUMO
The following is a report on one case of successful biopsy of a hepatic focal lesion incidentally found in an emergency computed tomography scan performed in a patient with acute liver failure clinical presentation. The presence of peri-hepatic ascites and severe coagulopathy contraindicated the percutaneous biopsy. The transjugular approach was used to perform a random liver biopsy to assess the amount of hepatic necrosis and to perform the focal lesion biopsy orienting the needle with sonography guidance. The specimen acquired was satisfactory to exclude the presence of malignant cells in the lesion; the diagnosis of atypical focal nodular hyperplasia was performed. The patient underwent successful liver transplantation the day after.
Assuntos
Hiperplasia Nodular Focal do Fígado/patologia , Falência Hepática Aguda/complicações , Fígado/patologia , Adulto , Biópsia por Agulha , Feminino , Hiperplasia Nodular Focal do Fígado/complicações , Humanos , Veias Jugulares , Falência Hepática Aguda/diagnóstico por imagem , RadiografiaRESUMO
Hemangiopericytoma (HP) is an uncommon vascular tumor that rarely develops in the liver. We present the case of a 68-year-old female with a primary HP involving the right lobe of the liver, detected during an abdominal screening sonography. The lesion was further evaluated using multidetector CT. The patient was treated with a right hepatectomy, and a pathologic diagnosis was made. Two years later, there was no evidence of recurrence.
Assuntos
Hemangiopericitoma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Idoso , Feminino , Hemangiopericitoma/patologia , Hemangiopericitoma/cirurgia , Hepatectomia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2 in the development and progression of various human cancers. Increasing evidence suggests that COX-1 may also play a similar role. Indeed, we have recently observed that the dual COX-1/COX-2 inhibitor indomethacin induces apoptosis in human hepatocellular carcinoma (HCC) cell lines more effectively than the selective COX-2 inhibitors, possibly implicating COX-1 in HCC. In this study we investigated the expression of COX-1 in non-tumor and malignant human liver tissues, as well as the effects of the highly selective COX-1 inhibitor SC-560 on cell growth and apoptosis in human HCC cell lines. Expression of COX-1 was detected in nearly all the samples assayed, although with a high variability between non-tumoral (NT) and malignant tissues. The percentage of COX-1 positive cells was significantly higher in the NT tissues than in the tumors (p<0.0001). In well-differentiated HCC COX-1 expression was significantly higher than in the poorly-differentiated tissues (p<0.05). SC-560 showed a dose- and time-dependent inhibitory effect on HCC cell growth. The combination of the COX-1 inhibitor with nimesulide and CAY10404, two selective COX-2 inhibitors, resulted in additive effects on cell growth inhibition. SC-560 also inhibited colony formation in soft agar and induced apoptosis in HCC cells in a dose-dependent manner. Moreover, SC-560 decreased the levels of the anti-apoptotic proteins survivin and XIAP and activated caspase-3 and -7 in a dose- and time-dependent fashion. In conclusion, we report for the first time that the selective COX-1 inhibitor SC-560 exhibits anti-tumor and apoptotic effects in human HCC cells. Overall, our previous and present results suggest that both COX-1 and COX-2 inhibitors may have potential therapeutic implications in HCC patients.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Ciclo-Oxigenase 1/metabolismo , Inibidores de Ciclo-Oxigenase/farmacologia , Pirazóis/farmacologia , Idoso , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Feminino , Regulação Enzimológica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genéticaRESUMO
The aim of this study is to identify the minimum safe amount of effective remnant liver volume (ERLV) in patients undergoing a major hepatectomy. Thirty-eight consecutive major hepatectomies (resection of > or = 3 Couinaud segments) performed between July 1999 and March 2004 in which a frozen section liver biopsy was obtained were included. No patient had chronic viral hepatitis, cirrhosis, or cholestasis. The total liver volume (TLV) was calculated using the Vauthey formula, and the postsurgical liver volume (PSLV) was derived by subtracting the estimated volume of liver resected from the TLV. The PSLV minus the percentage of macrovesicular steatosis as nonfunctional liver was defined as the effective remnant liver volume (ERLV). Three groups of ERLV/TLV ratios (<30%, between 30% and 60%, and >60%) were correlated with liver resection type, mortality, complications, intraoperative blood transfusions, operative time, length of hospitalization, and mean value of liver function tests in the first 5 postoperative days. Comparisons between clinical parameters were performed by Pearson chi2 test. There was significant correlation between ERLV/TLV ratios and surgical resection type (P < 0.001), early postoperative mortality (P < 0.01), and complications (P < 0.003). The ERLV/TLV ratio may be a useful predictor of surgical outcome after major hepatectomy.
Assuntos
Hepatectomia/efeitos adversos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/fisiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Fígado/patologia , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Tamanho do Órgão , Complicações Pós-Operatórias/diagnóstico , Probabilidade , Estudos Retrospectivos , Medição de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Altered pulmonary defenses in chronic obstructive pulmonary disease (COPD) may promote distal airways bacterial colonization. The expression/activation of Toll Like receptors (TLR) and beta 2 defensin (HBD2) release by epithelial cells crucially affect pulmonary defence mechanisms. METHODS: The epithelial expression of TLR4 and of HBD2 was assessed in surgical specimens from current smokers COPD (s-COPD; n = 17), ex-smokers COPD (ex-s-COPD; n = 8), smokers without COPD (S; n = 12), and from non-smoker non-COPD subjects (C; n = 13). RESULTS: In distal airways, s-COPD highly expressed TLR4 and HBD2. In central airways, S and s-COPD showed increased TLR4 expression. Lower HBD2 expression was observed in central airways of s-COPD when compared to S and to ex-s-COPD. s-COPD had a reduced HBD2 gene expression as demonstrated by real-time PCR on micro-dissected bronchial epithelial cells. Furthermore, HBD2 expression positively correlated with FEV1/FVC ratio and inversely correlated with the cigarette smoke exposure. In a bronchial epithelial cell line (16 HBE) IL-1ß significantly induced the HBD2 mRNA expression and cigarette smoke extracts significantly counteracted this IL-1 mediated effect reducing both the activation of NFkB pathway and the interaction between NFkB and HBD2 promoter. CONCLUSIONS: This study provides new insights on the possible mechanisms involved in the alteration of innate immunity mechanisms in COPD.
Assuntos
Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Fumar/efeitos adversos , Fumar/metabolismo , beta-Defensinas/metabolismo , Idoso , Sequência de Bases , Brônquios/metabolismo , Brônquios/patologia , Estudos de Casos e Controles , Linhagem Celular , Regulação para Baixo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fumar/genética , Receptor 4 Toll-Like/metabolismo , beta-Defensinas/genéticaRESUMO
Aim of this retrospective study is to evaluate accuracy and safety of transjugular liver biopsy using an 18-gauge automated core biopsy needle, in patients underwent liver transplantation. 183 consecutively transjugular liver biopsy were performed in 115 liver transplant patients. An 18-gauge automated core needle biopsy was used in all patients. Technical success was achieved in 182 procedures (99.5%). In one patient we were not able to obtain a liver sample. The mean number of passages was 1.43 (range 1-5). Mean number of fragments was 2 (range 1-12). Mean total length of the specimens was 1.7 cm (range 0.5-3.4 cm). The specimen was adequate for diagnosis in 172 (94.5%) cases and suboptimal or inadequate in 10 (4.5%). Suboptimal or inadequate samples were associated with higher number of passages (2.0 vs. 1.4, p<0.012), higher number of fragments (4.3 vs. 1.9, p<0.0001) and decreased total length of the specimens (0.99 vs. 1.73, p<0.03). As only complication one patient (0.5%) had a large perihepatic hematoma requiring blood transfusion. In conclusion using an 18-gauge automated core needle biopsy, in most liver transplant recipients, an accurate diagnosis can be obtained with one or two passages. This is associated with a low risk of complications.
Assuntos
Biópsia por Agulha Fina/instrumentação , Biópsia por Agulha Fina/métodos , Transplante de Fígado/patologia , Fígado/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Lactente , Veias Jugulares/diagnóstico por imagem , Fígado/diagnóstico por imagem , Transplante de Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Adulto JovemRESUMO
AIM: To evaluate radiofrequency thermal ablation (RTA) for treatment of cystic echinococcosis in animal models (explanted organs). METHODS: Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80 degrees C, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic. RESULTS: The subjects of the study were 17 cysts (nine hepatic and eight pulmonary), who were treated with RTA. Pathology showed 100% success rate in both hepatic (9/9) and lung cysts (8/8); immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts. CONCLUSION: RTA appears to be very effective in killing hydatid cysts of explanted liver and lung. Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in vivo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration, injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.
Assuntos
Ablação por Cateter , Equinococose Hepática/cirurgia , Equinococose Pulmonar/cirurgia , Echinococcus granulosus , Fígado/parasitologia , Pulmão/parasitologia , Animais , Bovinos , Equinococose Hepática/parasitologia , Equinococose Hepática/patologia , Equinococose Pulmonar/parasitologia , Equinococose Pulmonar/patologia , Humanos , Fígado/patologia , Pulmão/patologia , Projetos Piloto , Ovinos , TemperaturaRESUMO
Hepatic epithelioid haemangioendothelioma (HEHE) is extremely rare in children. We present an adolescent who presented with a scoliosis due to left thoracic pain. Multifocal HEHE was incidentally found during CT scan of the thorax, and confirmed with a multiphase CT scan of the abdomen, biopsy and immunochemistry. Left pleural and pulmonary involvement was suspected and later confirmed with biopsy and histopathological examination. The patient died 1 year after diagnosis. To the best of our knowledge, scoliosis has not previously been reported as the first symptom of EHE.
Assuntos
Hemangioendotelioma Epitelioide/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Meios de Contraste , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Achados Incidentais , Escoliose/diagnóstico por imagemRESUMO
The portal hyperperfusion, or small-for-size syndrome (SFSS), is a widely recognized clinical complication that may occur after segmental liver transplantation. Several surgical strategies have been proposed to reduce portal blood inflow and portal pressure after partial liver transplantation. In particular, splenic artery ligation and splenectomy have been used without a firm hemodynamic basis for these procedures. Our group recently demonstrated that, in patients with cirrhosis and portal hypertension, the occlusion of the splenic artery causes a significant reduction in the portal pressure gradient, which is directly related to the spleen volume and indirectly related to the liver volume. This concept is at the center of our strategy for performing early splenic artery embolization (SAE) for the treatment of SFSS after living-related liver transplantation (LRLT). Six patients developed small-for-size syndrome, defined as: onset within the first week after LRLT of progressive hyperbilirubinemia without mechanical cause; marked cholestasis; centrilobular sinusoidal dilatation and hepatocyte atrophy at liver biopsy; and refractory ascites in the absence of vascular complications. All six patients who underwent SAE rapidly improved their clinical condition, with an evident decrease in the value of bilirubin in the serum, in the production of ascites, and improvement in condition of pancytopenia. Coagulopathy expressed by the international normalized ratio value (INR) was not a reliable early marker of SFSS in this series; in fact a slight improvement in the result of this test was already present immediately after LRLT and before SAE. Because splenic flow clearly contributes to portal hyperperfusion, an early SAE can relieve the partial graft from the deleterious effect of this portal overflow.
Assuntos
Hipertensão Portal/etiologia , Transplante de Fígado/efeitos adversos , Fígado/anatomia & histologia , Doadores Vivos , Adulto , Anastomose Cirúrgica/efeitos adversos , Feminino , Seguimentos , Humanos , Hipertensão Portal/fisiopatologia , Hipertensão Portal/cirurgia , Ligadura/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Pressão na Veia Porta/fisiologia , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Artéria Esplênica/cirurgia , SíndromeRESUMO
PURPOSE: Acute liver failure (ALF) treated with conservative therapy has a poor prognosis, although individual survival varies greatly. In these patients, the eligibility for liver transplantation must be quickly decided. The aim of this study was to assess the role of transjugular liver biopsy (TJLB) in the management of patients with the clinical presentation of ALF. METHODS: Seventeen patients with the clinical presentation of ALF were referred to our institution during a 52 month period. A TJLB was performed using the Cook Quick-Core needle biopsy. Clinical data, procedural complications, and histologic findings were evaluated. RESULTS: Causes of ALF were virus hepatitis B infection in 7 patients, drug toxicity in 4, mushroom in 1, Wilson's disease in 1, and unknown origin in 4. TJLB was technically successful in all patients without procedure-related complications. Tissue specimens were satisfactory for diagnosis in all cases. In 14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3 patients the initial diagnosis was altered by the presence of unknown cirrhosis. Seven patients with necrosis < 60% were successfully treated with medical therapy; 6 patients with submassive or massive necrosis (> or = 85%) were treated with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had submassive necrosis. There was a strict statistical correlation (r = 0.972, p < 0.0001) between the amount of necrosis at the frozen section examination and the necrosis found at routine histologic examination. The average time for TJLB and frozen section examination was 80 min. CONCLUSION: In patients with the clinical presentation of ALF, submassive or massive liver necrosis and cirrhosis are predictors of poor prognosis. TLJB using an automated device and frozen section examination can be a quick and effective tool in clinical decision-making, especially in deciding patient selection and the best timing for liver transplantation.
Assuntos
Biópsia por Agulha , Falência Hepática Aguda/patologia , Adulto , Biópsia por Agulha/métodos , Feminino , Seguimentos , Humanos , Veias Jugulares , Cirrose Hepática/mortalidade , Cirrose Hepática/patologia , Cirrose Hepática/cirurgia , Falência Hepática Aguda/etiologia , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Masculino , Necrose Hepática Massiva/mortalidade , Necrose Hepática Massiva/patologia , Necrose Hepática Massiva/cirurgia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.
Assuntos
Rejeição de Enxerto/patologia , Transplante de Fígado/patologia , Fígado/patologia , Biópsia por Agulha , Diagnóstico Diferencial , Seguimentos , Humanos , Fatores de Tempo , Transplante HomólogoRESUMO
Recently, an atypical form of celiac disease (CD) has been identified, in which gastrointestinal symptoms are less pronounced. Other organs can be more or less severely affected, and the disease might be unrecognized and undiagnosed. In some cases, hypertransaminasemia has been indicated as the first symptom of CD in infancy. A direct relationship between liver damage and glutensensitivity has been proven by the disappearance of biochemical signs and histological lesions of the liver after the initiation of the gluten-free diet. The present case report is of a 14-year-old girl affected by CD and severe hepatic failure who underwent a liver transplant. To our knowledge, this case is the first report of liver involvement related to CD which is so severe as to require a liver transplant in a child. Because most patients with CD remain undiagnosed, and, as observed in the present report, untreated CD with subclinical hepatic involvement can lead to more serious liver disease, a more aggressive diagnostic work-up for CD in the general population is warranted.