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1.
Sci Rep ; 7(1): 17038, 2017 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-29213099

RESUMO

Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.


Assuntos
Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Animais , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Imagem de Difusão por Ressonância Magnética , Difenilamina/análogos & derivados , Difenilamina/uso terapêutico , Modelos Animais de Doenças , Humanos , Processamento de Imagem Assistida por Computador , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/metabolismo , Camundongos , Terapia Neoadjuvante , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Critérios de Avaliação de Resposta em Tumores Sólidos , Sulfonamidas/uso terapêutico , Neoplasias Pancreáticas
2.
Chirurg ; 88(3): 196-203, 2017 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-28054111

RESUMO

Esophageal diverticula are comparatively rare. The majority are Zenker's diverticula but parabronchial and epiphrenic diverticula can also occur. Parabronchial diverticula are of low clinical relevance, whereas Zenker's and epiphrenic diverticula both belong to the group of pulsion diverticula and can become clinically apparent by dysphagia and regurgitation. Approximately 100 years after the first surgical treatment, peroral approaches (e.g. stapler dissection and flexible endoscopic diverticulotomy) have now achieved a certain level of importance. Both approaches are less invasive than the open approach but are evidently more prone to recurrences. Accordingly, traditional open diverticulectomy with cervical myotomy should be recommended to patients with a reasonable life expectancy and an acceptable operative risk. This holds particularly true for Brombart stages I-III of the disease, as complete myotomy cannot be achieved via the peroral access. The classical surgical treatment of epiphrenic diverticula is open or laparoscopic/thoracoscopic diverticulectomy with distal myotomy, mostly combined with an anterior partial fundoplication; however, the leakage rate is high and several alternative options are currently being evaluated.


Assuntos
Divertículo Esofágico/cirurgia , Esfíncter Esofágico Inferior/cirurgia , Esofagoscopia/métodos , Fundoplicatura/métodos , Laparoscopia/métodos , Toracoscopia/métodos , Terapia Combinada , Divertículo Esofágico/diagnóstico , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Recidiva , Reoperação , Divertículo de Zenker/diagnóstico , Divertículo de Zenker/cirurgia
3.
Radiologe ; 49(2): 124-30, 2009 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-19107457

RESUMO

In recent years continuous advancements in software and hardware technology of modern MRI systems have contributed to substantial progress in the field of pancreatic tumor imaging. Despite technical advances in abdominal MRI, multislice CT still remains the preferential diagnostic tool for pancreatic lesions. In the majority of cases the essential clinical questions can thereby be answered with a high degree of accuracy. However, in dilemma cases state-of-the-art MR imaging can provide relevant information for the diagnosis allowing an optimal therapeutic concept. This report gives an overview on possible applications for MRI in the diagnostic evaluation of malignant pancreatic tumors.


Assuntos
Colangiopancreatografia por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Neoplasias Pancreáticas/diagnóstico , Diagnóstico Diferencial , Humanos , Laparoscopia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Estadiamento de Neoplasias , Pâncreas/patologia , Pâncreas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Sensibilidade e Especificidade
4.
Phys Rev E Stat Nonlin Soft Matter Phys ; 77(1 Pt 1): 011306, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18351849

RESUMO

An expression for the near-contact pair correlation function of D -dimensional weakly polydisperse hard spheres is presented, which arises from elementary free-volume arguments. Its derivative at contact agrees very well with our simulations for D=2 . For jammed states, the expression predicts that the number of exact contacts is equal to 2D, in agreement with established simulations. When the particles are wetted, they interact by the formation and rupture of liquid capillary bridges. Since formation and rupture events of capillary bonds are well separated in configuration space, the interaction is hysteretic with a characteristic energy loss Ecb. The pair correlation is strongly affected by this capillary interaction depending on the liquid-bond status of neighboring particles. A theory is derived for the nonequilibrium probability currents of the capillary interaction which determines the pair correlation function near contact. This finally yields an analytic expression for the equation of state, P=P(N/V,T), of wet granular matter for D=2, valid in the complete density range from gas to jamming. Driven wet granular matter exhibits a van der Waals-like unstable branch at granular temperatures T>T, is of relevance for aggregation in general, simulations have been performed which show very good agreement with the theoretically predicted coordination K of capillary bonds as a function of the bond length scrit. This result implies that particles that stick at the surface, scrit=0, form isostatic clusters. An extension of the theory in which the bridge coordination number K plays the role of a self-consistent mean-field is proposed.

5.
Phys Rev E Stat Nonlin Soft Matter Phys ; 75(6 Pt 1): 061301, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17677249

RESUMO

In this work we derive an analytic expression for the Kolmogorov-Sinai entropy of dilute wet granular matter, valid for any spatial dimension. The grains are modeled as hard spheres and the influence of the wetting liquid is described according to the capillary model, in which dissipation is due to the hysteretic cohesion force of capillary bridges. The Kolmogorov-Sinai entropy is expanded in a series with respect to density. We find a rapid increase of the leading term when liquid is added. This demonstrates the sensitivity of the granular dynamics to humidity, and shows that the liquid significantly increases the chaoticity of the granular gas.

6.
Phys Rev Lett ; 97(7): 078001, 2006 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-17026274

RESUMO

The free cooling of one-dimensional wet granular matter is presented in the framework of the minimal capillary model. We demonstrate analytically and by extensive simulations that above a critical density, the clustering of wet granular matter is not monotonic in time, but undergoes a sharp unclustering transition. This precipitation of granular droplets out of the gas takes place when the granular temperature comes close to the energy scale set by the capillary interaction.

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