21 research outputs found
Value of diffusion weighted MR imaging as an early surrogate parameter for evaluation of tumor response to high-dose-rate brachytherapy of colorectal liver metastases
<p>Abstract</p> <p>Background</p> <p>To assess the value of diffusion weighted imaging (DWI) as an early surrogate parameter for treatment response of colorectal liver metastases to image-guided single-fraction <sup>192</sup>Ir-high-dose-rate brachytherapy (HDR-BT).</p> <p>Methods</p> <p>Thirty patients with a total of 43 metastases underwent CT- or MRI-guided HDR-BT. In 13 of these patients a total of 15 additional lesions were identified, which were not treated at the initial session and served for comparison. Magnetic resonance imaging (MRI) including breathhold echoplanar DWI sequences was performed prior to therapy (baseline MRI), 2 days after HDR-BT (early MRI) as well as after 3 months (follow-up MRI). Tumor volume (TV) and intratumoral apparent diffusion coefficient (ADC) were measured independently by two radiologists. Statistical analysis was performed using univariate comparison, ANOVA and paired t test as well as Pearson's correlation.</p> <p>Results</p> <p>At early MRI no changes of TV and ADC were found for non-treated colorectal liver metastases. In contrast, mean TV of liver lesions treated with HDR-BT increased by 8.8% (<it>p </it>= 0.054) while mean tumor ADC decreased significantly by 11.4% (<it>p </it>< 0.001). At follow-up MRI mean TV of non-treated metastases increased by 50.8% (<it>p </it>= 0.027) without significant change of mean ADC values. In contrast, mean TV of treated lesions decreased by 47.0% (<it>p </it>= 0.026) while the mean ADC increased inversely by 28.6% compared to baseline values (<it>p </it>< 0.001; Pearson's correlation coefficient of r = -0.257; p < 0.001).</p> <p>Conclusions</p> <p>DWI is a promising imaging biomarker for early prediction of tumor response in patients with colorectal liver metastases treated with HDR-BT, yet the optimal interval between therapy and early follow-up needs to be elucidated.</p
Modified transarterial chemoembolization with locoregional administration of sorafenib for treating hepatocellular carcinoma: feasibility, efficacy, and safety in the VX-2 rabbit liver tumor model
PURPOSE:We aimed to assess the feasibility, efficacy and safety of a local application of sorafenib within a conventional transarterial chemoembolization in the VX-2 tumor-bearing rabbit model.METHODS:VX-2 tumors were induced in the left liver lobe of 10 New Zealand White rabbits. After two weeks, growth was verified by contrast-enhanced computed tomography (CT). Five rabbits were treated by transarterial chemoembolization using an emulsion of sorafenib and ethiodized oil (referred to as SORATACE; n=5). Rabbits receiving oral sorafenib for two weeks (n=2) and untreated rabbits (n=3) served as controls. After two weeks, contrast-enhanced CT was performed, followed by animal necropsy.RESULTS:The change in tumor diameter between baseline and follow-up was significantly different in the SORATACE group compared with the other groups; tumor shrinkage was observed in the SORATACE group only (P = 0.016). In both control groups, preserved hypervascularity was seen in the follow-up CT in all but one tumor. All tumors in the SORATACE group were devascularized in the follow-up CT. Importantly, substantial parenchymal damage in nontargeted areas of the tumor-bearing liver lobe was seen in rabbits treated with SORATACE.CONCLUSION:SORATACE demonstrated high efficacy in the treatment of experimental VX-2 liver tumors but was also associated with substantial liver parenchymal toxicity
Precipitating liquid embolics
GesamthabilitationsschriftPräzipitierende Flüssigembolisate zur Embolisation von zerebralen Aneurysmen
und arteriovenösen Malformationen basieren auf einer Mixtur aus biokompatiblen
Polymeren gelöst in organischen, wasserlöslichen Lösungsmitteln. Nach
intravaskulärer Injektion präzipitiert das Flüssigembolisat und bildet einen
nicht adhäsiven Ausguss infolge eines raschen Austauschs des Lösungsmittels
durch umgebende physiologische Flüssigkeiten. In der vorliegenden Arbeit wurde
die Entwicklung neuartiger präzipitierender Flüssigembolisate, welche sich aus
biokompatiblen Polymeren und darin gelösten organischen Lösungsmitteln
zusammensetzen, und der Einsatz der CT-Angiographie (CTA) zur Volumetrie von
embolisierten Aneurysmen dargestellt. Folgende Ergebnisse konnten hierbei
erzielt werden: 1\. Jodierter Polyvinyl Alkohol (I-PVAL) stellt einen in der
Arbeitsgruppe entwickelten Polymer-Bestandteil für präzipitierende
Flüssigembolisate dar. Wesentliche Innovation dieses Polymers gegenüber
bekannten Embolisaten ist die intrinsische Röntgensichtbarkeit ohne Zusatz
weiterer röntgendichter Substanzen. Eine Vorbereitung vor der Applikation ist
dadurch nicht notwendig. Wir konnten zeigen, dass mit einer zähflüssigen
Mixtur aus I-PVAL gelöst in Dimethylsulfoxid (DMSO), der meistverwendeten
Trägersubstanz präzipitierender Flüssigembolisate, die Embolisation
experimenteller breitbasiger Seitwandaneurysmen der Arteria carotis des
Schweins mit einer hohen initialen Okklusionsrate technisch möglich ist.
Darüber hinaus ist I-PVAL das erste neuroendovaskuläre Embolisationsmaterial
mit dem eine artefaktfreie Darstellung embolisierter Aneurysmen mittels CT und
MRT möglich ist. 2\. Aus toxikologischer Sicht bestehen Bedenken bezüglich der
Verwendung von DMSO als Lösungsmittel-Bestandteil präzipitierender
Flüssigembolisate. Anlass für Besorgnis ist insbesondere ein nach zu rascher
intraarterieller Injektion auftretender Vasospasmus, welcher in Untersuchungen
am Rete mirabile des Schweins regelhaft fatale klinische Folgen hatte. In
einer vergleichenden tierexperimentellen Studie am Rete mirabile konnten wir
andere organische Lösungsmittel identifizieren, welche eine wesentlich
geringere Angiotoxizität nach intraarterieller Injektion als DMSO aufwiesen.
Die Substanzen mit den günstigsten angiotoxischen Profilen waren hierbei
Dimethylsulfoxid (DMI) und N-Methyl Pyrrolidon (NMP). 3\. In der Arbeitsgruppe
wurde ein weiteres Flüssigembolisat synthetisiert, welches die aufgezeigten
Vorzüge des intrinsisch röntgendichten Polymers I-PVAL mit jenen des gering
angiotoxischen Lösungsmittels NMP verbindet. Aufgrund der guten und homogenen
Röntgensichtbarkeit auch unter Fluoroskopie sowie günstiger
Präzipitationseigenschaften war auch mit dieser Polymer-Lösungsmittel-Mixtur
die Embolisation experimenteller breitbasiger Seitwandaneurysmen der Arteria
carotis des Schweins mit einer hohen initialen Okklusionsrate technisch
möglich. 4\. In einer in vitro Studie mit verschiedenen Phantomen
intrakranieller Aneurysmen zeigte sich die moderne Mehrzeilen CTA geeignet zur
exakten Volumenbestimmung auch solcher komplexer dreidimensionaler Strukturen.
Die geringsten Abweichungen fanden sich hierbei für Volumen Rendering
Rekonstruktionen unter Verwendung einer automatisierten Analysesoftware. 5\.
Bei der Volumetrie mittels CTA von experimentellen Aneurysmen, welche direkt
im Anschluss an deren chirurgische Konstruktion mit I-PVAL embolisiert wurden,
zeigte sich eine deutliche Volumenzunahme von durchschnittlich über 60%. Diese
Beobachtung war jedoch am ehesten durch eine Unzulänglichkeit des
Aneurysmamodells bedingt. Bedenken einer Druckerhöhung im Aneurysma durch die
Embolisatinjektion während der temporären Ballonokklusion des Trägergefäßes
konnten durch weitere in vitro Versuche mit intraaneurysmatischer Druckmessung
ausgeräumt werden. Ursache hierfür sind trotz maximal inflatiertem Ballon
stets verbleibende Öffnungen entlang des Mikrokatheters, welche auf der
anderen Seite jedoch die bevorzugte Austrittsstelle von Embolisat in das
Trägergefäß darstellen.Precipitating liquid embolics used for embolization of cerebral aneurysms or
arteriovenous malformations are based on solutions of preformed polymers
dissolved in organic, water-miscible solvents. Following intravascular
injection, the liquid embolic precipitates and forms a nonadhesive solid cast
due to a rapid exchange of the solvent with surrounding physiological fluids.
We have developed a new precipitating liquid embolic, composed of a
biocompatible polymer dissolved in organic solvents. In addition, we have
evaluated CT-angiography (CTA) for volumetry of such embolized aneurysms. The
following results were achieved: 1\. Iodinated polyvinyl alcohol (I-PVAL)
resembles a newly developed polymer proportion of precipitating liquid
embolics. The main innovation of this polymer in comparison to known embolics
is the intrinsic radiopacity without the need of radiopaque admixtures. Thus,
no preparation before use is necessary. We have demonstrated that embolisation
of porcine carotid artery sidewall aneurysms with a highly viscous mixture of
I-PVAL dissolved in dimethylsulfoxide (DMSO), the most commonly used organic
solvent for precipitating liquid embolics, was feasible with a high initial
occlusion rate. Moreover, I-PVAL is the first neuroendovascular embolisation
material not to produce artifacts on CT or MRI of embolized aneurysms. 2\.
Concerns exist for the use of DMSO as a solvent proportion of precipitating
liquid embolics from a toxicological standpoint. Especially worrisome is the
observation that rapid intraarterial injection in swine rete mirabile
regularly lead to vasospasm with fatal clinic consequences. In a comparative
study in swine rete mirabile we were able to identify other organic solvents,
which were far less angiotoxic than DMSO after intraarterial injection. The
substances with the most promising angiotoxic profiles were dimethylsulfoxide
(DMI) and n-methyl pyrrolidone (NMP). 3\. We have synthesized another liquid
embolic, which combines the advantages of the intrinsically radiopaque polymer
I-PVAL with those of the low angiotoxic solvent NMP. We have demonstrated that
embolisation of porcine carotid artery sidewall aneurysms was feasible with a
high initial occlusion rate due to the good and homogeneous radiopacity and
favourable precipitation pattern of this liquid embolic. 4\. A systematic in
vitro analysis of different reconstruction methods for volume determination of
phantoms of intracranial aneurysms using 16-row multislice CTA was performed.
This was the first investigation to show that volumetric assessment of such
complex three dimensional structures is feasible with CTA. The lowest
deviations were found for an automated volume analysis tool on volume-rendered
reconstructions. 5\. A considerable volume increase of over 60% of
experimental aneurysms, which were embolized with I-PVAL immediately after
their surgical construction, was found by CTA volumetry. This observation was
most likely the result of a shortcoming of this aneurysm model. The concern of
an intraaneurysmal pressure increase during injection of liquid embolics and
temporary balloon occlusion of the parent artery was ruled out by in-vitro
experiments with assessment of intraaneurysmal pressure. On the other hand,
open spaces along the microcatheter remain despite maximal inflation of a
compliant balloon, which constitute the preferred route of liquid embolic
migration into the parent artery
CT-assisted transfemoral intrahepatic portosystemic shunt in a long duration follow-up : a case report
Background: Transjugular intrahepatic portosystemic shunt (TIPS) in patients with portal hypertension may be considered as a rescue therapy in case of recurrent variceal bleeding or failure of endoscopic management. Case Reports: We present a case of a patient with massive gastroesophageal variceal bleeding refractory to numerous endoscopic treatments in which TIPS was considered in an attempt to decrease the risk of potentially fatal rebleeding. Standard TIPS procedure was not feasible due to altered anatomy of the liver resulting from right hemidiaphragmatic paresis. Computed Tomography (CT) fluoroscopic guidance was utilized for direct percutaneous puncture of the left hepatic and left portal vein with subsequent guidewire snaring to perform portosystemic shunting via femoral access. Since the procedure, no recurrent variceal bleeding was reported and the shunt remained patent at a 3-year follow-up. Although stent fracture with fragment migration was observed. Conclusions: Significant variation in liver anatomy does not preclude the creation of nonsurgical portosystemic shunt. In these cases, combined percutaneous and endovascular technique may be utilized
Validation of VX2 as a Hepatocellular Carcinoma Model: Comparison of the Molecular Reaction of VX2 and HepG2 Tumor Cells to Sorafenib In Vitro
As there is currently no superior hepatocellular carcinoma (HCC) model with percutaneous vascular access for transarterial treatments available, the VX2 rabbit model is frequently used for in vivo investigations on liver carcinoma. However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1 beta (IL1 beta). Phosphorylation of protein kinase B (AKT) the mitogen-activated protein kinases (MAPKs) p38 and p42/44 (extracellular signal-regulated kinase, ERK1/2) and inhibitor of kappa light chain gene enhancer alpha (I kappa B alpha) was determined by western blotting as these events are associated with early signaling cascades. Additionally, the inhibition of phosphorylation under sorafenib treatment was investigated. Sorafenib was equally toxic to both cell lines, but only in HepG2 was activation of caspase 3/7 activity, as a sign of apoptosis, observed. VX2 cells exhibited generally more intense phosphorylation signals in response to the growth factors and also serum. In contrast to VX2, HepG2 cells showed no response to PDGF-AB or VEGF as determined by kinase phosphorylation. In both cell lines, sorafenib inhibited growth factor-induced phosphorylation of ERK and p38-MAPK. AKT phosphorylation was only inhibited in VX2 cells and I kappa B alpha phosphorylation was not influenced by this kinase inhibitor in either cell type. Taken together, the two cellular models for HCC share several features related to sorafenib application, but differed in their responsiveness towards growth factors. Therefore, results obtained with the VX2 model cannot be extended to human HCC without appropriate caution
Common clonal origin of an acute B-lymphoblastic leukemia and a Langerhans’ cell sarcoma: evidence for hematopoietic plasticity
Background. The hierarchical organization of the hematopoiesis with unidirectional lineage determination has become a questionable tenet in view of the experimental evidence for reprogramming and transdifferentiation of lineage determined cells. Clinical examples of hematopoietic lineage plasticity are rare. Here we report on a patient who presented with an acute B-lymphoblastic leukemia (B-ALL) and developed a Langerhans cell sarcoma (LCS) nine years later. We provide evidence that the second neoplasm is the result of a transdifferentiation. Design and Methods. B-ALL was diagnosed in an 11 year old boy in 1996. Treatment according to the ALL-BFM-1995 protocol resulted in a complete remission. Nine years later, in 2005, LCS was diagnosed in a supraclavicular lymph node. Despite treatment with different chemotherapy protocols the patient had progressive disease. Finally, he received an allogeneic peripheral blood stem cell transplantation and achieved a continuous remission. Molecular studies of IgH- and TCRgamma- gene rearrangements were performed with DNA from the LCS and the cryopreserved cells from the B-ALL. The expression of PAX5 and Id2 was analyzed with real-time RT-PCR. Results. Identical IgH-rearrangements in the B-ALL and the LCS were demonstrated. The key factors required for B-cell and dendritic cell development PAX5 and Id2 were differentially expressed, with a strong PAX5 signal in the B-ALL and only a weak expression in the LCS, whereas Id2 showed an opposite pattern. Conclusions. The identical IgH-rearrangement in both neoplasms indicates a transdifferentiation of the B-ALL into a LCS. Loss of PAX5 and the acquisition of Id2 suggest that these key factors are involved in the transdifferentiation from a B-cell phenotype into a Langerhans/dendritic cell phenotype