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1.
Liver Int ; 43(4): 878-887, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36797990

RESUMO

BACKGROUND: Novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (elexacaftor/tezacaftor/ivacaftor-ETI) promise clinically significant and sustained improvements for patients with cystic fibrosis (CF). In this study, we investigated the impact of ETI therapy on liver stiffness and bile acid metabolism in a cohort of children and young adults with CF. METHODS: A prospective observational study (NCT05576324) was conducted from September 2020 to November 2021 enrolling CF patients naive to ETI. Standard laboratory chemistry, sweat test, lung function, share wave velocity (SWV) derived by acoustic radiation force impulse imaging (ARFI) and serum bile acid profiles were assessed before and 6 months after induction of ETI therapy. RESULTS: A total of 20 patients (10 aged <20 years) completed the study. While lung function and BMI improved after ETI therapy, ARFI SWV increased in CF patients <20 years of age (from 1.27 to 1.43 m/s, p = 0.023). Bile acid (BA) profiles revealed a decrease in unconjugated (5.75 vs 1.46, p = 0.007) and increase in glycine-conjugated derivatives (GCDCA) (4.79 vs 6.64 p = 0.016). There was a positive correlation between ARFI SWV values and GCDCA (r = 0.80, p < 0.0001). Glycine-conjugated BA provided high diagnostic accuracy to predict increased ARFI measurements (AUC 0.90) and clinical (Colombo) CFLD grading (AUC 0.97). CONCLUSIONS: ARFI SWV and bile acid profiles provide evidence for early increase in liver stiffness and altered bile acid metabolism in young CF patients after initiation of ETI and may serve as synergistic measures for detection of hepatic complications during ETI therapy.


Assuntos
Fibrose Cística , Técnicas de Imagem por Elasticidade , Humanos , Criança , Adulto Jovem , Adulto , Fibrose Cística/tratamento farmacológico , Fibrose Cística/complicações , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Técnicas de Imagem por Elasticidade/métodos , Cognição , Fígado/diagnóstico por imagem , Mutação
2.
Ultraschall Med ; 44(6): 606-613, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36781161

RESUMO

OBJECTIVES: Hepatocellular carcinoma (HCC) upon contrast-enhanced ultrasound (CEUS) typically shows arterial phase hyperenhancement (APHE), followed by late (> 60 seconds) and mild contrast washout (WO). Although APHE is considered as the hallmark of HCC, it can be absent in some HCCs. Thus, we explored which sonomorphological and histopathological features of HCC are associated with a lack of APHE upon CEUS. METHODS: Focal liver lesions in high-risk patients for HCC were assessed with CEUS following a standardized protocol in a prospective multi-center real-life setting. CEUS patterns in HCC were assessed, and tumour and patient characteristics were compared for HCCs with and without APHE. RESULTS: 316 patients with HCC were recruited (cirrhosis, 76.9%). APHE occurred in 271/316 HCCs (85.8%). A lack of APHE was associated with portal vein thrombosis, tumour infiltration of the liver vessels (p<0.001), larger size, multilocularity, and higher depth location upon ultrasound (p<0.01). Histological grading did not differ between HCCs with and without APHE (p=0.39). Histopathological features of HCCs without APHE included cirrhotic stromal reaction, marked tumour cell steatosis and absence of the typical surrounding dilated sinusoidal vascular channels. CONCLUSION: Correlation with histopathological findings support the fact that HCCs with a lack of APHE in CEUS are a heterogeneous group. The examiner has to be aware that particularly HCCs with portal vein thrombosis or macro-invasion of the liver vessels may lack APHE.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Estudos Prospectivos , Meios de Contraste , Ultrassonografia/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
3.
Ann Hepatol ; 18(1): 23-29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31113596

RESUMO

INTRODUCTION: Acoustic Radiation Force Impulse (ARFI) elastography evaluates hepatic fibrosis non-invasively and has been mainly validated in viral hepatitis. Data on rare liver diseases such as autoimmune hepatitis (AIH), overlap syndrome, primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) are sparse. MATERIAL AND METHODS: 85 patients (including 31 AIH, 26 PBC, 16 PSC and 3 PSC-and 9 PBC-AIH-overlap syndromes) were retrospectively analysed pointing at ARFI elastography of the liver and the correlation with histologic Ishak fibrosis score (F0-6). Results of shear wave velocities (m/s) were expressed as mean ± standard deviation. RESULTS: The mean shear wave velocity of all 85 patients showed 1.80 ± 0.84 m/s (0.74-3.98). The ARFI elastography values correlated with the degree of fibrosis in all patients overall and in patients with AIH, overlap syndrome and PSC, respectively. The subgroup of 26 patients with PBC (only with Ishak F > 3) revealed no correlation between ARFI and these early fibrosis stages (r = 0.019, p = 0.927). ARFI elastography correlated with bilirubin, AST, but not with patient age, body mass index or measurement depth. The cut-off of 2.04 m/s for detecting cirrhosis (Ishak F > 5) leads to a sensitivity of 90.0% and specificity of 74.7% (AUROC 87.2%). CONCLUSION: ARFI elastography can evaluate fibrosis in AIH, PSC and PSC-/PBC-AIH-overlap syndrome with good accuracy for the detection of hepatic cirrhosis. Shear wave velocities in PBC should be interpreted with caution in early stages of fibrosis.


Assuntos
Acústica , Colestase/diagnóstico , Técnicas de Imagem por Elasticidade/métodos , Hepatite Autoimune/diagnóstico , Hepatopatias/diagnóstico , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Adulto Jovem
4.
Ultraschall Med ; 40(4): 404-424, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31382313

RESUMO

Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy in the assessment of focal liver lesions. Clinical context (presence of liver cirrhosis, history of other malignancy versus incidental finding) is crucial for the correct interpretation of CEUS findings. CEUS has to be preceded by structured anamnesis and clinical examination as well as accurate B-mode sonography. Metastases are the most common malignant liver lesions in a non-cirrhotic liver. According to their contrast enhancement in the arterial phase, metastases are categorized as hyper- and hypo-vascular metastases. A common feature of all metastatic lesions is washout of the contrast agent in the portal venous or late phase. In the context of liver cirrhosis, > 95 % of focal liver lesions are hepatocellular carcinomas (HCCs). HCCs typically show arterial phase hyperenhancement, followed by mild and gradual contrast washout occurring very late in the late phase. For intrahepatic cholangiocellular carcinoma (ICC), the pattern of contrast enhancement in the arterial phase can vary. However, all ICCs typically show early and pronounced washout. Other liver malignancies like lymphoma, angiosarcoma, epithelioid hemangioendothelioma and others are very rare. Except for the contrast washout seen in all liver malignancies, they do not display pathognomonic enhancement patterns upon CEUS. Thus, biopsy is indispensable for definite diagnosis of the tumor entity. Furthermore, CEUS is used for the detection of metastases and therapeutic monitoring after local ablative procedures. The examination procedure differs slightly depending on the specific indication (characterization, detection).


Assuntos
Carcinoma Hepatocelular , Meios de Contraste , Neoplasias Hepáticas , Ultrassonografia , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/métodos
6.
Eur Radiol ; 28(10): 4254-4264, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29675659

RESUMO

OBJECTIVES: We compared the interobserver agreement for the recently introduced contrast-enhanced ultrasound (CEUS)-based algorithm CEUS-LI-RADS (Liver Imaging Reporting and Data System) versus the well-established magnetic resonance imaging (MRI)-LI-RADS for non-invasive diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. METHODS: Focal liver lesions in 50 high-risk patients (mean age 66.2 ± 11.8 years; 39 male) were assessed retrospectively with CEUS and MRI. Two independent observers reviewed CEUS and MRI examinations, separately, classifying observations according to CEUS-LI-RADSv.2016 and MRI-LI-RADSv.2014. Interobserver agreement was assessed with Cohen's kappa. RESULTS: Forty-three lesions were HCCs; two were intrahepatic cholangiocarcinomas; five were benign lesions. Arterial phase hyperenhancement was perceived less frequently with CEUS than with MRI (37/50 / 38/50 lesions = 74%/78% [CEUS; observer 1/observer 2] versus 46/50 / 44/50 lesions = 92%/88% [MRI; observer 1/observer 2]). Washout appearance was observed in 34/50 / 20/50 lesions = 68%/40% with CEUS and 31/50 / 31/50 lesions = 62%/62%) with MRI. Interobserver agreement was moderate for arterial hyperenhancement (ĸ = 0.511/0.565 [CEUS/MRI]) and "washout" (ĸ = 0.490/0.582 [CEUS/MRI]), fair for CEUS-LI-RADS category (ĸ = 0.309) and substantial for MRI-LI-RADS category (ĸ = 0.609). Intermodality agreement was fair for arterial hyperenhancement (ĸ = 0.329), slight to fair for "washout" (ĸ = 0.202) and LI-RADS category (ĸ = 0.218) CONCLUSION: Interobserver agreement is substantial for MRI-LI-RADS and only fair for CEUS-LI-RADS. This is mostly because interobserver agreement in the perception of washout appearance is better in MRI than in CEUS. Further refinement of the LI-RADS algorithms and increasing education and practice may be necessary to improve the concordance between CEUS and MRI for the final LI-RADS categorization. KEY POINTS: • CEUS-LI-RADS and MRI-LIRADS enable standardized non-invasive diagnosis of HCC in high-risk patients. • With CEUS, interobserver agreement is better for arterial hyperenhancement than for "washout". • Interobserver agreement for major features is moderate for both CEUS and MRI. • Interobserver agreement for LI-RADS category is substantial for MRI, and fair for CEUS. • Interobserver-agreement for CEUS-LI-RADS will presumably improve with ongoing use of the algorithm.


Assuntos
Algoritmos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ultrassonografia/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
7.
Acta Radiol ; 59(10): 1149-1156, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29345146

RESUMO

Background Microvascularization of the bowel wall can be visualized and quantified non-invasively by software-assisted analysis of derived time-intensity curves. Purpose To perform software-based quantification of bowel wall perfusion using quantitative contrast-enhanced ultrasound (CEUS) according to clinical response in patients with inflammatory bowel disease treated with vedolizumab. Material and Methods In a prospective study, in 18 out of 34 patients, high-frequency ultrasound of bowel wall thickness using color Doppler flow combined with CEUS was performed at baseline and after 14 weeks of treatment with vedolizumab. Clinical activity scores at week 14 were used to differentiate between responders and non-responders. CEUS parameters were calculated by software analysis of the video loops. Results Nine of 18 patients (11 with Crohn's disease and seven with ulcerative colitis) showed response to treatment with vedolizumab. Overall, the responder group showed a significant decrease in the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS parameters of mural microvascularization such as peak enhancement or wash-in rate decreased in responders, in contrast with non-responders. Time-derived parameters remained stable or increased during treatment in all patients. Conclusion Analysis of bowel microvascularization by CEUS shows statistically significant changes in the wash-in-rate related to response of vedolizumab therapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ultrassonografia Doppler em Cores , Adulto , Biomarcadores/sangue , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos , Projetos Piloto , Estudos Prospectivos , Software , Hexafluoreto de Enxofre
8.
Clin J Sport Med ; 28(4): 332-338, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28708711

RESUMO

OBJECTIVE: To emphasize the diagnostic value of contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries with different degrees of severity by comparing findings to established imaging modalities such as conventional ultrasound and magnetic resonance imaging (MRI). DESIGN: Case series. SETTING: Institutional study. Conventional ultrasound and CEUS were performed in the Department of Internal Medicine. Magnetic resonance imaging was carried out in the Department of Radiology within the Magnetom Avanto 1.5T and Magnetom Skyra fit 3T (Siemens Healthineers, Erlangen, Germany) and in the Institution of Imaging Diagnostics and Therapy (Magnetom Avanto 1.5T; Siemens, Erlangen, Germany). PATIENTS: Fifteen patients who underwent an acute muscle injury were recruited. MAIN OUTCOME MEASURES: The appearance and detectable size of muscle injuries were compared between each imaging modality. The injuries were assessed by 3 independent observers and blinded between imaging modalities. RESULTS: All 15 injuries were identified on MRI and CEUS, whereas 10 injuries showed abnormalities in conventional ultrasound. The determination and measurement revealed significant differences between conventional ultrasound and CEUS depending on injury severity. Contrast-enhanced ultrasound revealed an impairment of microcirculation in grade I lesions (corresponding to intramuscular edema observed in MRI), which was not detectable using conventional ultrasound. CONCLUSIONS: Our results indicate that performing CEUS seems to be a sensitive additional diagnostic modality in the early assessment of muscle injuries. Our results highlight the advantages of CEUS in the imaging of low-grade lesions when compared with conventional ultrasound, as this was the more accurate modality for identifying intramuscular edema.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/lesões , Ultrassonografia/métodos , Adolescente , Adulto , Meios de Contraste , Edema/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Projetos Piloto , Adulto Jovem
9.
Ultraschall Med ; 39(6): 667-674, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29879746

RESUMO

OBJECTIVES: This pilot study aimed at assessing interobserver agreement with two contrast-enhanced ultrasound (CEUS) algorithms for the diagnosis of hepatocellular carcinoma (HCC) in high-risk patients. METHODS: Focal liver lesions in 55 high-risk patients were assessed independently by three blinded observers with two standardized CEUS algorithms: ESCULAP (Erlanger Synopsis of Contrast-Enhanced Ultrasound for Liver Lesion Assessment in Patients at risk) and ACR-CEUS-LI-RADSv.2016 (American College of Radiology CEUS-Liver Imaging Reporting and Data System). Lesions were categorized according to size and ultrasound contrast enhancement in the arterial, portal-venous and late phase. Interobserver agreement for assessment of enhancement pattern and categorization was compared between both CEUS algorithms. Additionally, diagnostic accuracy for the definitive diagnosis of HCC was compared. Histology and/or CE-MRI and follow-up served as reference standards. RESULTS: 55 patients were included in the study (male/female, 44/ 11; mean age: 65.9 years). 90.9 % had cirrhosis. Histological findings were available in 39/55 lesions (70.9 %). Reference standard of the 55 lesions revealed 48 HCCs, 2 intrahepatic cholangiocellular carcinomas (ICCs), and 5 non-HCC-non-ICC lesions. Interobserver agreement was moderate to substantial for arterial phase hyperenhancement (ĸ = 0.53 - 0.67), and fair to moderate for contrast washout in the portal-venous or late phase (ĸ = 0.33 - 0.53). Concerning the CEUS-based algorithms, the interreader agreement was substantial for the ESCULAP category (ĸ = 0.64 - 0.68) and fair for the CEUS-LI-RADS® category (ĸ = 0.3 - 0.39). Disagreement between observers was mostly due to different perception of washout. CONCLUSION: Interobserver agreement is better for ESCULAP than for CEUS-LI-RADS®. This is mostly due to the fact that perception of contrast washout varies between different observers. However, interobserver agreement is good for arterial phase hyperenhancement, which is the key diagnostic feature for the diagnosis of HCC with CEUS in the cirrhotic liver.


Assuntos
Algoritmos , Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Variações Dependentes do Observador , Projetos Piloto , Ultrassonografia
10.
Curr Rheumatol Rep ; 19(10): 62, 2017 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-28844095

RESUMO

PURPOSE OF REVIEW: Polyarthritis can have numerous reasons and may thus constitute a challenge for differential diagnosis. One rare potential reason for sterile polyarthritis is underlying pancreatic disease with systemic hyperlipasemia, most often accompanied by painful skin lesions caused by a subcutaneous inflammatory process known as panniculitis. Systematic evidence on pancreatic panniculitis and polyarthritis is limited, particularly regarding its feature as facultative paraneoplasia with underlying intra- or even extra-pancreatic malignancy. Therefore, we will summarize the current knowledge about this orphan disease including epidemiological, pathophysiological, diagnostic, and treatment aspects in the present review. RECENT FINDINGS: Although direct evidence is lacking, it is highly probable that pancreatic polyarthritis and panniculitis are caused by peripheral lipolytic activity of lipase systemically circulating due to benign (e.g., acute or chronic pancreatitis) or malign (e.g., acinar cell carcinoma (ACC) or adenocarcinoma) pancreatic disease. In the latter case, pancreatic polyarthritis and panniculitis are associated with poor outcome. Pancreatic polyarthritis and panniculitis should always be included into diagnostic considerations, and once suspected, a thorough work-up to identify the underlying disease has to be performed.


Assuntos
Artrite/fisiopatologia , Pancreatopatias/fisiopatologia , Paniculite/fisiopatologia , Artrite/diagnóstico , Artrite/epidemiologia , Artrite/terapia , Humanos , Lipase/sangue , Pancreatopatias/diagnóstico , Pancreatopatias/epidemiologia , Pancreatopatias/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/terapia , Paniculite/diagnóstico , Paniculite/epidemiologia , Paniculite/terapia , Prognóstico
11.
Med Sci Monit ; 23: 1483-1492, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28348359

RESUMO

BACKGROUND Pancreatic intraductal papillary mucinous neoplasms (IPMNs) present a clinical challenge. Evidence-based guidelines are lacking. The so-called "Fukuoka criteria" were developed to assess the risk of malignancy in IPMNs upon imaging. However, little is known about their diagnostic value and the natural course of IPMNs. Thus, the aim of this study was the assessment of Fukuoka criteria and patient management in pancreatic IPMNs -during follow-up. MATERIAL AND METHODS IPMNs were identified via retrospective survey of endoscopic ultrasound (EUS) examinations. Fukuoka criteria were assessed on EUS findings and additional imaging (CT, MRI, ultrasound). Patients' symptoms and comorbidities were recorded. Dynamics of Fukuoka criteria and patient management were compared at first presentation and during follow-up. RESULTS We screened 1324 EUS examinations. Sixty-five patients (male/female, 14/37; mean age, 68.8 years; range, 48-85 years) with IPMNs were identified (57 branch duct (BD-)IPMNs, 3 main duct (MD-) IPMNs, 5 mixed-type (MT)-IPMNs). Seven patients received surgical resection (4 BD-IPMNs, 2 MD-IPMNs, 1 MT-IPMN). Nine BD-IPMNs had neither surgery nor follow-up. Fifty-one patients (44 BD-IPMNs, 2 MD-IPMNs, 5 MT-IPMNs) underwent follow-up (mean duration, 18.7 months; range, 3-139 months). There were 15/51 patients who were initially Fukuoka-positive. One MD-IPMN, 4/5 MT-IPMNs, and 13/44 BD-IPMNs showed progressive changes but were not resected due to patients' refusal or comorbidities. Four BD-IPMNs converted to Fukuoka-positive. CONCLUSIONS Evidence-based guidelines for non-invasive dignity assessment of IPMNs are lacking. In our study, MD-IPMNs displayed greater dynamics than BD-IPMNs and MT-IPMNs concerning Fukuoka criteria. Prospective long-term studies are needed to clarify prognostic significance of the single Fukuoka criteria and sensible duration of follow-up.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Assistência ao Paciente , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Endossonografia , Seguimentos , Guias como Assunto , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Encaminhamento e Consulta
13.
Gut ; 65(1): 134-43, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25524262

RESUMO

INTRODUCTION: Radiofrequency ablation (RFA), a palliative therapeutic option for solid hepatic tumours, stimulates localised and systemic antitumour cytotoxic T cells. We studied how far addition of CpG B oligonucleotides, toll like receptor (TLR) 9 agonists, would increase the antitumoural T cell response of RFA in the highly aggressive VX2 hepatoma. METHODS: Rabbits were randomised to receive RFA, CpG B, their combination or no therapy. The antitumour efficacy of RFA alone or in combination with CpG B was further tested by rechallenging a separate group with intravenously injected VX2 tumour cells after 120 days. Animals were assessed for survival, tumour size and spread, and tumour and immune related histological markers after 120 days. Peripheral blood mononuclear cells were tested for tumour-specific T cell activation and cytotoxicity. Immune modulatory cytokines tumour necrosis factor α, interleukin (IL)-2/IL-8/IL-10/IL-12 and interferon γ, and vascular endothelial growth factor were measured in serum. RESULTS: Mean survival of untreated animals was 36 days, as compared with 97, 78 and 114 days for RFA, CpG and combination therapy, respectively. Compared with untreated controls, antitumour T cell stimulation/cytotoxicity increased 26/16-fold, 32/17-fold and 50/38-fold 2 weeks after RFA, CpG and combination treatments, respectively. The combination inhibited tumour spread to lungs and peritoneum significantly and prohibited new tumour growth in animals receiving a secondary systemic tumour cell injection. RFA alone induced a Th1 cytokine pattern, while IL-8 and IL-10 were only upregulated in CpG treated animals and controls. CONCLUSIONS: The combination of TLR9 stimulation with RFA resulted in a potentiated antitumour T cell response and cytotoxicity in the VX2 tumour model. Only this combination prevented subsequent tumour spread and resulted in a significantly improved survival, justifying the need for further exploration of the combination of ablative therapies and TLR9 agonists in liver cancer.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Ablação por Cateter , Neoplasias Hepáticas Experimentais/terapia , Neoplasias Hepáticas/terapia , Oligodesoxirribonucleotídeos/uso terapêutico , Animais , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/mortalidade , Neoplasias Hepáticas Experimentais/patologia , Transplante de Neoplasias , Coelhos , Distribuição Aleatória , Linfócitos T Citotóxicos/metabolismo , Receptor Toll-Like 9/agonistas , Resultado do Tratamento
14.
BMC Cancer ; 16: 130, 2016 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-26895632

RESUMO

BACKGROUND: Pancreatic panniculitis is a rare condition, which has only been described in relation with pancreatic diseases up to now. It is characterized by necrotizing subcutaneous inflammation and is thought to be triggered by adipocyte necrosis due to systemic release of pancreatic enzymes with consecutive infiltration of neutrophils. We present the first case of a patient with pancreatic panniculitis caused by pancreatic-type primary acinar cell carcinoma (ACC) of the liver and without underlying pancreatic disease. CASE PRESENTATION: A 73-year old Caucasian female patient was referred to our department with painful cutaneous nodules persisting for eight weeks and with marked lipasemia (~15000 U/l; normal range <60 U/l). Four weeks prior, several liver lesions had been detected. Empiric treatment with steroids did not show any effect. A biopsy of the skin nodules revealed "pancreatic" panniculitis, while abdominal imaging with ultrasound, computed tomography and magnetic resonance imaging detected no abnormal pancreatic findings. Ultrasound-guided biopsy of the liver lesions showed infiltrates of an ACC. The patient died soon thereafter. Autopsy failed to reveal any other primary for the ACC, so that a pancreatic-type ACC of the liver was diagnosed by exclusion. One hundred thirty cases of pancreatic panniculitis published within the last 20 years are reviewed. ACC of the pancreas is the most common underlying neoplastic condition. Patients with associated neoplasm are significantly older, take longer to be diagnosed and have higher lipase levels than patients with underlying pancreatitis. Extrapancreatic pancreatic-type ACC is very rare, but shows the same biological features as ACC of the pancreas. It is believed to develop from metaplastic or ectopic pancreatic tissue. Up to now, no pancreatic panniculitis in extrapancreatic ACC has been described. CONCLUSION: Pancreatic panniculitis should always be included in the differential diagnosis of lipolytic panniculitic lesions. It can be regarded as a facultative paraneoplastic phenomenon. When suspected, a thorough work-up for identification of the underlying disease is mandatory and extrapancreatic lesions (e.g. liver) should also be considered. While administration of octreotide or steroids can sometimes alleviate symptoms, immediate treatment of the associated condition is the only effective management option.


Assuntos
Carcinoma de Células Acinares/diagnóstico , Neoplasias Hepáticas/diagnóstico , Pâncreas/patologia , Paniculite/etiologia , Dermatopatias/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Carcinoma de Células Acinares/complicações , Criança , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Paniculite/patologia , Dermatopatias/patologia , Adulto Jovem
15.
Med Sci Monit ; 22: 3500-3505, 2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27690214

RESUMO

BACKGROUND Non-invasive procedures such as acoustic radiation force impulse imaging (ARFI) shear-wave elastography are currently used for the assessment of liver fibrosis. In the course of chronic hepatitis C, significant liver fibrosis or cirrhosis develops in approximately 25% of patients, which is a negative predictor of antiviral treatment response. Cirrhosis can be prevented by successful virus elimination. In this prospective study, a pretreatment ARFI cutoff value of 1.5 m/s was evaluated in relation to sustained virological response to anti-HCV therapy. MATERIAL AND METHODS In 23 patients with chronic hepatitis C, liver stiffness was examined with ARFI at defined times before and under antiviral triple therapy (peginterferon, ribavirin in combination with a first-generation protease inhibitor, and telaprevir or boceprevir). Patients were stratified into 2 groups based on pretreatment ARFI values (<1.5 m/s and ≥1.5 m/s) for the assessment of virological response. RESULTS The liver stiffness at baseline for all patients was 1.57±0.79 m/s (ARFI median ± standard deviation; margin: 0.81 m/s to 3.45 m/s). At week 4 of triple therapy, patients with low pretreatment ARFI values had higher rates of HCV-RNA negativity (69% vs. 43%), reflecting an early rapid virological response (eRVR). Sustained virological response (SVR) was found in 75% (12/16) of patients with an ARFI value <1.5 m/s and only 57% (4/7) of patients with ARFI value ≥1.5 m/s. CONCLUSIONS Patients with chronic hepatitis C and pretreatment ARFI <1.5 m/s showed earlier virus elimination and better response to treatment.

19.
Med Sci Monit ; 20: 2027-35, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25342166

RESUMO

BACKGROUND: Acoustic radiation force impulse (ARFI) elastography is a reliable diagnostic device for quantitative non-invasive assessment of liver fibrosis in patients with chronic liver disease. The aim of our prospective study was to evaluate the impact of ARFI in patients after orthotopic liver transplantation (OLT). Therefore, we compared ARFI shear wave velocities with clinical features, non-invasive markers, and the histology of patients following OLT. MATERIAL AND METHODS: Post-transplant patients underwent a clinical examination and blood samples were taken. B-mode and Doppler ultrasound (US) of the portal vein and the hepatic artery were performed. Subsequently, a minimum of 10 valid ARFI values were measured in the left and right liver lobe. Liver biopsy was performed if indicated. RESULTS: Between May 2012 and May 2014, 58 Patients after OLT were included in the prospective study. Laboratory markers and aspartate aminotransferase-to-platelet ratio index (APRI) correlated with ARFI values (r=0.44, p<0.001). The histological (n=22) fibrosis score (Ludwig) was significantly correlated with the ARFI of the biopsy site (r=0.55, p=0.008). The mean shear-wave velocities were significantly increased in advanced fibrosis (F≤2 1.57±0.57 m/s; F≥3 2.85±0.66 m/s; p<0.001), obstructive cholestasis and active viral hepatitis. The area under the receiver operating characteristic (AUROC) curves for the accuracy of ARFI were 74% (F≥1), 73% (F≥2), 93% (F≥3), and 80% (=F4). CONCLUSIONS: ARFI elastography correlates well with laboratory values and with noninvasive and invasive markers of fibrosis in patients after OLT. In this regard, elevated ARFI-velocities should be interpreted with caution in the context of obstructive cholestasis and active viral disease.


Assuntos
Acústica , Transplante de Fígado , Adulto , Idoso , Aspartato Aminotransferases/sangue , Biópsia , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade
20.
Acad Radiol ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38378326

RESUMO

RATIONALE AND OBJECTIVES: There are currently no studies investigating the in vivo stiffness of the most commonly used autografts for anterior cruciate ligament reconstruction (ACLR) using Shear wave elastography (SWE). We hypothesize that there are differences regarding the elastic properties between the three tendons commonly used for ACLR and that they are influenced by patient-related factors. MATERIALS AND METHODS: 80 healthy subjects (25 females, 55 males, age: 25.33 ± 4.76 years, BMI: 23.76 ± 3.14 kg/m2, 40 semiprofessional athletes, athlete group [AG], age: 25.51 [19-29]; 40 healthy controls, control group [CG], age: 25.50 [20-29]) were recruited as participants. In addition to patient reported outcome scores, every participant underwent a standardized multimodal ultrasound protocol consisting of B-mode-ultrasound (B-US), Color Doppler-ultrasound (CD-US) and a SWE examination of the bilateral quadriceps tendon (QT), patellar tendon (PT) and semitendinosus tendon (ST). RESULTS: The highest shear wave velocity (SWV) were observed in ST (4.88 (4.35-5.52) m/s, ST vs QT, p = 0.005; ST vs PT, p < 0.001) followed by QT (4.61 (4.13-5.26) m/s, QT vs PT, p < 0.001) and PT (3.73 (3.30-4.68) m/s). Median QT, PT and ST stiffness was significantly higher in AG compared to CG. Male subjects tend to have stiffer QT and PT than female subjects. Positive correlation with SWV was obtained for age and activity level. CONCLUSION: There are significant differences regarding in vivo tendon stiffness between the most frequently used autograft tendon options for ACLR. The quantitative information obtained by SWE could be of particular interest for graft choice for ACLR.

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