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1.
Cardiovasc Intervent Radiol ; 44(1): 141-149, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32895782

RESUMO

PURPOSE: To determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach. METHODS: Utilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands. RESULTS: A total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5-2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p < 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia. CONCLUSIONS: PEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study.


Assuntos
Sistemas de Liberação de Medicamentos , Óleo Etiodado/administração & dosagem , Pâncreas/efeitos dos fármacos , Animais , Antineoplásicos/administração & dosagem , Infusões Intravenosas , Modelos Animais , Pressão , Suínos
2.
J Vasc Interv Radiol ; 31(10): 1697-1705.e3, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32773247

RESUMO

PURPOSE: To develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ferumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models. RESULTS: DOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion. CONCLUSIONS: SC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Meios de Contraste/administração & dosagem , Doxorrubicina/administração & dosagem , Óleo Etiodado/administração & dosagem , Óxido Ferroso-Férrico/administração & dosagem , Neoplasias Hepáticas Experimentais/terapia , Colato de Sódio/administração & dosagem , Animais , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Meios de Contraste/química , Doxorrubicina/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Emulsões , Óxido Ferroso-Férrico/química , Infusões Intra-Arteriais , Cinética , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/patologia , Imageamento por Ressonância Magnética , Imagem Multimodal , Ratos Sprague-Dawley , Colato de Sódio/química , Tomografia Computadorizada por Raios X
3.
Radiology ; 295(2): 458-466, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32208098

RESUMO

Background Abnormalities of the central lymphatic system (CLS) are increasingly treated by interventional radiology approaches. Planning of these procedures, however, is challenging because of the lack of clinical imaging tools. Purpose To evaluate the clinical usefulness of contrast agent-enhanced interstitial transpedal MR lymphangiography in the preinterventional workup of lymphatic interventions in patients with thoracic chylous effusions. Materials and Methods Patients with chylous effusions evaluated from January 2014 and December 2017 were included in this retrospective analysis of transpedal MR lymphangiography. Indications were chylothorax (n = 19; 76%), cervical lymphatic fistula (n = 2; 8%), and combined chylothorax and chylous ascites (n = 4; 16%). Patients underwent transpedal MR lymphangiography at 1.5 T with T1-weighted imaging after interstitial pedal of gadolinium-based contrast medium under local anesthesia. Contrast-enhanced MRI was evaluated for technical success, depiction of pathologic abnormalities of the CLS, and access site for lymphatic interventions (ie, clinically useful examination). Reader agreement for image quality and overall degree of visualization was assessed with weighted κ. Interrelations between overall image quality and degree of visualization of CLS structures were assessed by Spearman ρ. Efficacy of transpedal MR lymphangiography was calculated by using radiographic lymphangiography as the reference standard. Results Twenty-five patients (mean age, 54 years ± 18 [standard deviation]; 13 men) were evaluated. Eight percent (two of 25) of examinations failed (lymphoma in one patient and technical failure in one patient). Contrast agent injection was well tolerated without complications. Interrater agreement of image quality was excellent (κ = 0.96). The degree of CLS visualization correlated with overall image quality (ρ = 0.71; P < .001). Retroperitoneal lymphatics, cisterna chyli, and thoracic duct were viewed with an accuracy of 23 of 25 (92%), 24 of 25 (96%), and 23 of 25 (92%), respectively. Anatomic variations, a lymphatic pathologic abnormality, and interventional access routes were identified with an accuracy of 22 of 25 (88%), 23 of 25 (92%), and 24 of 25 (96%), respectively. Overall, 23 of 25 (92%) transpedal MR lymphangiograms provided clinically useful information. Conclusion Transpedal interstitial MR lymphangiography was well tolerated by the patient and identified specific pathologic abnormalities causing thoracic chylous leakages before lymphatic intervention. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Maki and Itkin in this issue.


Assuntos
Quilotórax/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Óleo Etiodado/administração & dosagem , Sistema Linfático/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite Quilosa/diagnóstico por imagem , Feminino , , Humanos , Injeções Intradérmicas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
J Cancer Res Clin Oncol ; 146(4): 1033-1050, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32107625

RESUMO

PURPOSE: Several scoring systems have been proposed to predict the outcome of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). However, the application of these scores to a bridging to transplant setting is poorly validated. Evaluation of the applicability of prognostic scores for patients undergoing TACE in palliative intention vs. bridging therapy to liver transplantation (LT) is necessary. METHODS: Between 2008 and 2017, 148 patients with HCC received 492 completed TACE procedures (158 for bridging to transplant; 334 TACE procedures in palliative treatment intention at our center and were analyzed retrospectively. Scores (ART, CLIP, ALBI, APRI, SNACOR, HAP, STATE score, Child-Pugh, MELD, Okuda and BCLC) were calculated and evaluated for prediction of overall survival. ROC analysis was performed to assess prediction of 3-year survival and treatment discontinuation. RESULTS: In patients receiving TACE in palliative intention most scores predicted OS in univariate analysis but only mSNACOR score (p = 0.006), State score (p < 0.001) and Child-Pugh score (p < 0.001) revealed statistical significance in the multivariate analysis. In the bridging to LT cohort only the BCLC score revealed statistical significance (p = 0.002). CONCLUSIONS: Clinical usability of suggested scoring systems for TACE might be limited depending on the individual patient cohorts and the indication. Especially in patients receiving TACE as bridging to LT none of the scores showed sufficiently applicability. In our study Child-Pugh score, STATE score and mSNACOR score showed the best performance assessing OS in patients with TACE as palliative therapy.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/estatística & dados numéricos , Estudos de Coortes , Doxorrubicina/administração & dosagem , Óleo Etiodado/administração & dosagem , Feminino , Alemanha/epidemiologia , Humanos , Neoplasias Hepáticas/mortalidade , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
6.
PLoS One ; 15(1): e0227711, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935255

RESUMO

Locoregional therapies for hepatocellular carcinoma (HCC) include endovascular treatments such as chemoembolization (TACE) and bland embolization (TAE). TACE is the most adopted technique, despite a lack of definitive evidence of superiority over TAE, which is less costly and better tolerated due to the absence of chemotherapy. However, few studies have reported data on TAE monotherapy for unresectable HCC. We report our results in a cohort of 230 patients with unresectable HCC treated with TAE (TAE with 40-100micron microparticles, TAE with microparticles plus n-butyl-2-cyanoacrylate, TAE with Lipiodol) over the course of seven years. Thirty-seven patients (14%) were down-staged during observation and also received a percutaneous ablation. We observed 1-, 2-, 3-, 4- and 5-year rates of 84,8%, 58,7%, 38,3%, 28,3%, and 18,7%. Patients who also received percutaneous treatment performed best. Our results broaden the body of evidence for the use of TAE in advanced HCC.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Quimioembolização Terapêutica/métodos , Óleo Etiodado/administração & dosagem , Óleo Etiodado/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
7.
J Laparoendosc Adv Surg Tech A ; 30(3): 299-303, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31971877

RESUMO

Purpose: To improve the tumor localization during laparoscopic surgery, we describe an innovative technique involving superselective intra-arterial injection of blue dye in tumoral vessels to color the tumor before surgical enucleation. Materials and Methods: The dye injection was performed at the same time as superselective embolization, immediately before laparoscopic surgery in a hybrid operating room. We used this new treatment sequence on 50 consecutive patients. Results: The selective intra-arterial injection of an emulsion of blue dye and lipiodol was feasible in 46 (92%) cases and well tolerated, followed by superselective embolization of the tumor vessels with glue or coils. The tumor was easily localized during surgery due to the blue coloration. Tumor coloration was not associated with postoperative complication, especially allergic reaction or renal failure. Pathologic analysis of the tumor was not modified by the coloration and all tumors had negative surgical margins. Conclusions: The preoperative dye localization is a feasible, safe, and accurate procedure. This combined approach reduces the difficulty of surgery and increases patient safety.


Assuntos
Carcinoma de Células Renais/terapia , Corantes/administração & dosagem , Embolização Terapêutica/métodos , Neoplasias Renais/terapia , Laparoscopia/métodos , Nefrectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/patologia , Terapia Combinada , Cianoacrilatos/administração & dosagem , Óleo Etiodado/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Imageamento Tridimensional , Injeções Intra-Arteriais , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Salas Cirúrgicas , Corantes de Rosanilina/administração & dosagem , Carga Tumoral
8.
PLoS One ; 15(1): e0227972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995589

RESUMO

PURPOSE: The purpose of this study is to evaluate the use of density measurements in the diagnosis of an underlying residual tumor beyond iodine depositions after Lipiodol-based conventional transarterial chemoembolization (cTACE). METHOD AND MATERIALS: Thirty follow-up CT scans of 20 patients 6-12 weeks after Lipiodol-based cTACE, receiving a digital subtraction angiography at the same time, were analyzed. Reference for the detection of a residual tumor was the angiography, and a visible contrast enhancement was categorized as a residual tumor (n = 16 with residual tumor; n = 14 without residual tumor). The density of the iodine depositions was measured in all containing slices in non-contrast-, arterial- and portal venous-phase CT scans, with a slice thickness of 5.00 mm. The mean density of the iodine deposition during the portal venous phase was subtracted from the mean density of the arterial phase to calculate the density changes (a positive enhancement score represents washout in the portal venous phase). In addition, a quotient relating to the non-contrast measurement was evaluated. RESULTS: Patients with a residual tumor displayed significantly higher enhancement scores in favor of density reduction between the arterial and portal venous phases, compared to patients without a residual tumor (1.41 ± 3.59, n = 14 vs. -13.97 ± 2.88, n = 16; p-value < 0.01). Furthermore, 87.75% of patients with an enhancement score higher than -1.00 (n = 9) had a residual tumor, whereas 100.00% of patients with an enhancement score lower than -20.00 (n = 6) were shown to be tumor-free. The enhancement score quotient resulted in similar findings. CONCLUSION: After cTACE in patients with hepatocellular carcinoma (HCC), the presence of a viable tumor correlated with enhancement scores based on the density measurements of iodine depositions in different phases of the CT scan. Low enhancement scores were associated with completely treated tumors and can aid the decision process to avoid possibly unnecessary angiographies.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Iodo/isolamento & purificação , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasia Residual/diagnóstico , Angiografia , Artérias/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Meios de Contraste/administração & dosagem , Meios de Contraste/isolamento & purificação , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Iodo/administração & dosagem , Neoplasias Hepáticas/patologia , Masculino , Neoplasia Residual/diagnóstico por imagem , Neoplasia Residual/patologia , Veia Porta/diagnóstico por imagem , Tomografia Computadorizada por Raios X
9.
Cardiovasc Intervent Radiol ; 43(3): 423-433, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31720806

RESUMO

OBJECTIVE: To investigate technical factors affecting local tumor control of small hepatocellular carcinoma (HCC) treated by superselective conventional transarterial chemoembolization (cTACE) using lipiodol and to compare prognoses between groups with and without these factors. MATERIALS AND METHODS: Sixty-three consecutive patients with 73 HCC nodules (diameter, 1-3 cm) treated by cTACE were retrospectively analyzed. A positive or a negative 3D-safety margin was defined as a ≥ 1-mm area of lipiodol accumulation or as a diameter of lipiodol accumulation < 1 mm in liver parenchyma surrounding the tumor using plain CT images obtained within a week after TACE. Uni- and multivariate analyses were performed to identify technical factors determining local tumor control rate. Subgroup analysis of survival rates in treatment-naïve patients was performed according to the detected factors. RESULTS: In univariate analyses, three-dimensional (3D)-safety margin and portal vein visualization were associated with local tumor control rates. In multivariate analysis, only positive 3D-safety margin remained a significant contributor (p = 0.001). Two-year cumulative local disease-free survival rates with positive and negative 3D-safety margin were 82.8% and 19.3%, respectively (p = 0.001). In subgroup survival analysis of the 36 newly diagnosed patients, the 1-, 2-, 3-, 4-, and 5-year cumulative OS rates for patients with and without positive margins were 100% versus 100%, 96.4% versus 75.0%, 81.8% versus 62.5%, 74.4% versus 41.7%, and 47.0% versus 0%, respectively (median survival time; 57.6 months vs. 37.1, p = 0.047). CONCLUSION: Obtaining a 3D-safety margin can suppress local tumor recurrence and prolong survival in superselective cTACE for small HCC.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Imageamento Tridimensional/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
10.
Gen Thorac Cardiovasc Surg ; 68(1): 87-90, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760567

RESUMO

Preoperative marking is necessary in thoracoscopic wedge resections of lung nodules expected to be invisible or nonpalpable during surgery. Recently, lidocaine gel was added to a dye solution containing indigo carmine and lipiodol to promote micelle formation, but the optimal mixing ratio was not determined. Thus, an in vitro experiment was performed to identify the optimal mixing ratio of lidocaine gel, indigo carmine and lipiodol. To fixed volumes of indigo carmine and lipiodol of 0.5 ml each, 0.1, 0.2, 0.3, 0.4 and 0.5 ml of lidocaine gel was added. Changes were examined every 2 h. No changes were seen in the mixtures containing 0.1 and 0.2 ml of lidocaine gel, whereas those with 0.3, 0.4 and 0.5 ml had clearly separated after 2 h. Our findings suggest that the ideal proportion of indigo carmine, lipiodol and lidocaine gel for use in preoperative marking is 5:5:2.


Assuntos
Óleo Etiodado/administração & dosagem , Índigo Carmim/administração & dosagem , Lidocaína/administração & dosagem , Cirurgia Torácica Vídeoassistida/métodos , Administração Cutânea , Corantes , Géis , Humanos , Cuidados Pré-Operatórios
11.
Clin Cancer Res ; 26(2): 428-438, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582517

RESUMO

PURPOSE: To establish magnetic resonance (MR)-based molecular imaging paradigms for the noninvasive monitoring of extracellular pH (pHe) as a functional surrogate biomarker for metabolic changes induced by locoregional therapy of liver cancer. EXPERIMENTAL DESIGN: Thirty-two VX2 tumor-bearing New Zealand white rabbits underwent longitudinal imaging on clinical 3T-MRI and CT scanners before and up to 2 weeks after complete conventional transarterial chemoembolization (cTACE) using ethiodized oil (lipiodol) and doxorubicin. MR-spectroscopic imaging (MRSI) was employed for pHe mapping. Multiparametric MRI and CT were performed to quantify tumor enhancement, diffusion, and lipiodol coverage of the tumor posttherapy. In addition, incomplete cTACE with reduced chemoembolic doses was applied to mimic undertreatment and exploit pHe mapping to detect viable tumor residuals. Imaging findings were correlated with histopathologic markers indicative of metabolic state (HIF-1α, GLUT-1, and LAMP-2) and viability (proliferating cell nuclear antigen and terminal deoxynucleotidyl-transferase dUTP nick-end labeling). RESULTS: Untreated VX2 tumors demonstrated a significantly lower pHe (6.80 ± 0.09) than liver parenchyma (7.19 ± 0.03, P < 0.001). Upregulation of HIF-1α, GLUT-1, and LAMP-2 confirmed a hyperglycolytic tumor phenotype and acidosis. A gradual tumor pHe increase toward normalization similar to parenchyma was revealed within 2 weeks after complete cTACE, which correlated with decreasing detectability of metabolic markers. In contrast, pHe mapping after incomplete cTACE indicated both acidic viable residuals and increased tumor pHe of treated regions. Multimodal imaging revealed durable tumor devascularization immediately after complete cTACE, gradually increasing necrosis, and sustained lipiodol coverage of the tumor. CONCLUSIONS: MRSI-based pHe mapping can serve as a longitudinal monitoring tool for viable tumors. As most liver tumors are hyperglycolytic creating microenvironmental acidosis, therapy-induced normalization of tumor pHe may be used as a functional biomarker for positive therapeutic outcome.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/análise , Glicólise , Neoplasias Hepáticas Experimentais/patologia , Imagem Molecular/métodos , Microambiente Tumoral , Animais , Doxorrubicina/administração & dosagem , Óleo Etiodado/administração & dosagem , Concentração de Íons de Hidrogênio , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Imageamento por Ressonância Magnética/métodos , Masculino , Coelhos
12.
Minim Invasive Ther Allied Technol ; 29(2): 98-106, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30821547

RESUMO

Purpose: To compare the efficacy of right portal vein embolization using ethylene vinyl alcohol (EVOH-PVE) compared to other embolic agents and surgical right portal vein ligation (PVL).Material and methods: Patients with right sided liver malignancies scheduled for extensive surgery and receiving induction of liver hypertrophy via right portal vein embolization/ligature between 2010-2016 were retrospectively evaluated. Treatments included were ethylene vinyl alcohol copolymer (Onyx®, EVOH-PVE), ethiodized oil (Lipiodol®, Lipiodol/PVA-PVE), polyvinyl alcohol (PVA-PVE) or surgical ligature (PVL). Liver segments S2/3 were used to assess hypertrophy. Primary outcome was future liver remnant growth in ml/day.Results: Forty-one patients were included (EVOH-PVE n = 11; Lipiodol/PVA-PVE n = 10; PVA-PVE n = 8; PVL n = 12), the majority presenting with cholangiocarcinoma and colorectal metastases (n = 11; n = 27). Pre-interventional liver volumes were comparable (p = .095). Liver hypertrophy was successfully induced in all but one patient receiving Lipiodol/PVA-PVE. Liver segment S2/3 growth was largest for EVOH-PVE (5.38 ml/d) followed by PVA-PVE (2.5 ml/d), with significantly higher growth rates than PVL (1.24 ml/d; p < .001; p = .007). No significant difference was evident for Lipiodol/PVA-PVE (1.43 ml/d, p = .809).Conclusions: Portal vein embolization using EVOH demonstrates fastest S2/3 growth rates compared to other embolic agents and PVL, potentially due to its permanent portal vein embolization and induction of hepatic inflammation.


Assuntos
Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Veia Porta/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Óleo Etiodado/administração & dosagem , Feminino , Hepatectomia , Humanos , Hipertrofia , Ligadura , Masculino , Pessoa de Meia-Idade , Álcool de Polivinil/administração & dosagem , Polivinil/administração & dosagem , Estudos Retrospectivos
13.
J Oncol Pharm Pract ; 26(2): 507-510, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31315548

RESUMO

Hepatocellular carcinoma is the fourth leading cause of cancer death. For unresectable intermediate-stage hepatocellular carcinoma, the standard treatment is transarterial chemoembolization. To date, the overall survival at three years remains low, and there is currently no consensus about the best anticancer agent and optimal treatment regimen. We report the case of a hepatocellular carcinoma patient with a vascular contraindication to embolization who achieved a complete response after four intra-arterial infusions of idarubicin emulsified with lipiodol. The patient maintained his response over a three-year period without any hepatocellular carcinoma treatment, demonstrating the major role of the anticancer agent in the efficacy of transarterial therapies for intermediate-stage hepatocellular carcinoma.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Óleo Etiodado/administração & dosagem , Idarubicina/administração & dosagem , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Carcinoma Hepatocelular/diagnóstico , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Resultado do Tratamento
14.
J Vasc Interv Radiol ; 31(2): 347-351, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31542274

RESUMO

PURPOSE: To evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits. MATERIALS AND METHODS: Epirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24). Next, 0.5 mL of emulsion was injected into the hepatic artery, followed by embolization using 100-300-µm microspheres. The serum epirubicin concentrations (immediately after, 5 minutes after, and 10 minutes after) and the tumor epirubicin concentrations (20 minutes after and 48 hours after) were measured after transarterial chemoembolization. Histopathologic evaluation was performed with a fluorescence microscope. RESULTS: The area under the curve and maximum concentrations of epirubicin in plasma were 0.45 ± 0.18 µg min/mL and 0.13 ± 0.06 µg/mL, respectively, in the device group and 0.71 ± 0.45 µg min/mL and 0.22 ± 0.17 µg/mL, respectively, in the 3-way-stopcock group (P = .013 and P = .021, respectively). The mean epirubicin concentrations in VX2 tumors at 48 hours in the device group and the 3-way-stopcock group were 13.7 ± 6.71 and 7.72 ± 3.26 µg/g tissue, respectively (P = .013). The tumor necrosis ratios at 48 hours were 62 ± 11% in the device group and 51 ± 13% in the 3-way-stopcock group (P = .039). CONCLUSIONS: Conventional transarterial chemoembolization using the pumping emulsification device significantly improved the pharmacokinetics of epirubicin compared to the current standard technique using a 3-way stopcock.


Assuntos
Antibióticos Antineoplásicos/farmacocinética , Quimioembolização Terapêutica/instrumentação , Epirubicina/farmacocinética , Vidro , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Membranas Artificiais , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/sangue , Emulsões , Epirubicina/administração & dosagem , Epirubicina/sangue , Desenho de Equipamento , Óleo Etiodado/administração & dosagem , Neoplasias Hepáticas Experimentais/sangue , Neoplasias Hepáticas Experimentais/patologia , Necrose , Porosidade , Coelhos
15.
BMC Cancer ; 19(1): 1162, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783814

RESUMO

BACKGROUND: To compare the efficacy and safety between conventional transarterial chemoembolization (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with infiltrative hepatocellular carcinoma (iHCC). METHODS: A total of 89 iHCC patients who were treated with either cTACE (n = 33) or DEB-TACE (n = 56) between April 2013 and September 2017 were included in this retrospective study. Patients with the situations that might have a poor outcome were defined as advanced disease including Child-Pugh class B, bilobar lesions, tumor size greater than 10 cm, ECOG 1-2, tumor burden of 50-70%, and the presence of ascites, arterioportal shunt (APS), and portal venous tumor thrombus (PVTT). The tumor response was measured 1-month and 3-month after the procedure. Progression-free survival (PFS) was calculated. Toxicity was graded by Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0). The differences in tumor response, PFS, and toxicity were compared between the DEB-TACE group and cTACE group. RESULTS: At 1-month and 3-month after the procedure, the objective response rate (ORR) in the overall study population was similar in DEB-TACE group and cTACE group. The disease control rate (DCR), at 1-month after the procedure, was significantly higher in the patients treated with DEB-TACE relative to those treated with cTACE (P = 0.034), while after 3 months, the difference did not differ between two groups. DEB-TACE showed a higher DCR than cTACE in patients with tumor size greater than 10 cm (P = 0.036) or associated with APS (P = 0.030) at 1-month after the procedure, while after 3 months, the difference was only noted in patients with APS (P = 0.036). The median PFS in DEB-TACE group was 96 days, while in cTACE group was 94 days, and there was no difference in PFS between two groups (P = 0.831). In the side effect analysis, abdominal pain (P = 0.034) and fever (P = 0.009) were more frequently present in the cTACE group than DEB-TACE group, but there was no difference in high grade liver toxicity between the two groups. CONCLUSIONS: Compared to cTACE, DEB-TACE offers slightly better DCR and tolerability for iHCC patients, particularly in patients associated with APS and large tumor size. However, DEB-TACE does not provide higher PFS than cTACE.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/química , Carcinoma Hepatocelular/patologia , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/química , Avaliação de Medicamentos , Óleo Etiodado/administração & dosagem , Óleo Etiodado/efeitos adversos , Óleo Etiodado/química , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Microesferas , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
16.
Lima; Instituto Nacional de Salud; dic. 2019.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1130013

RESUMO

INTRODUCCIÓN: Los tumores hepáticos se pueden dividir en benignos y malignos. El tumor hepático benigno sólido más frecuente es el hemangioma seguido de la hiperplasia nodular focal, y el tumor quístico simple. Por otro lado, el tumor hepático maligno primario más frecuente es la hepatocarcinoma (HC). A. Cuadro clínico Los únicos tratamientos disponibles como cura potencial para el HC son el trasplante hepático y resección. Varias terapias locoregionales han sido usadas ampliamente para manejar a los pacientes con HC avanzado o como terapia puente para pacientes con enfermedad temprana e intermedia. Dentro de estas terapias, la terapia de quimioembolización convencional (TACE) usa como agente quimiembólico al aceite iodinado de amapola o lipiodol como un agente para embolizacion intra-arterial debido a su viscosidad e insolubilidad en el agua. B. Tecnología sanitária El aceite iodado de Amapola (adormidera), también conocido como "lipiodol" es un éster etílico de los ácidos grasos yodados del aceite de amapola. El aceite iodado es un producto de adición yodado de un aceite o aceites vegetales, que contiene el 30-42% de yodo orgánico combinado. Es estéril, insoluble en agua, soluble en éter, cloroformo o bencina de petróleo. Se usa como medio de contraste para estudios como histerosalpingografia, linfografia, sialografía y como uso selectivo intra-arterial hepático con diagnostico conocido de HC (para estudio y para quimio-embolizaciones). En el presente documento, cada vez que se mencione TACE convencional, se referirá a TACE utilizando lipiodol o aceite de amapola. OBJETIVO: Evaluar la eficacia y seguridad, así como documentos relacionados a la decisión de cobertura del aceite iodado de amapola para quimio embolización selectiva de pacientes con tumores hepáticos. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas: MEDLINE, LILACS, COCHRANE, así como en buscadores genéricos de Internet incluyendo Google Scholar y TRIPDATABASE. Adicionalmente, se hizo una búsqueda dentro de la información generada por las principales instituciones internacionales de oncología y agencias de tecnologías sanitarias que realizan revisiones sistemáticas (RS), evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC). RESULTADOS: Se seleccionó una RS, un estudio observacional comparativo. Además, se seleccionaron dos GPC. No se encontraron ETS ni evaluaciones económicas regionales. CONCLUSIONES: La evidencia comparativa del uso de aceite de amapola para quimioembolización en tumores hepática es escasa. Basado en un estudio comparativo no se evidencia diferencia entre TACE convencional y del TACE con partículas cargadas con agente terapéutico. Comparado com intervenciones de cuidados paliativos, TACE convencional ofrece una alta supervivencia, enfermedad libre de progresión, entre otros. Dos GPC recomiendan el uso de TACE convencional para tratamiento de tumores no resecables. Sin embargo, consideran que TACE con partículas cargadas con agente terapéutico podría ser una opción beneficiosa en comparación del TACE convencional con aceite de amapola.


Assuntos
Humanos , Quimioembolização Terapêutica/instrumentação , Óleo Etiodado/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Peru , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício
17.
BMC Cancer ; 19(1): 1126, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747895

RESUMO

BACKGROUND: TAE-gene therapy for hepatoma, incorporating the tumor-targeted therapeutic efficacy of trans-arterial embolization, hydroxyapatite nanoparticles (nHAP) and anti-cancer wild-type p53 gene (wt-p53), was presented in our former studies (Int J Nanomedicine 8:3757-68, 2013, Liver Int 32:998-1007, 2012). However, the incompletely antitumoral effect entails defined guidelines on searching properer materials for this novel therapy. METHODS: Unmodified nHAP, Ca(2+) modified nHAP, poly-lysine modified nHAP and liposome were separately used to form U-nanoplex, Ca-nanoplex, Pll-nanoplex, L-nanoplex respectively with wt-p53 expressing plasmid. The four nanoplexs were then applied in vitro for human normal hepacyte L02 and hepatoma HePG2 cell line, and in vivo for rabbits with hepatic VX2 tumor by injection of nanoplexs/lipiodol emulsion into the hepatic artery in a tumor target manner. The distribution, superficial potential, physical structure, morphology and chemical compositions of nanoplexs were evaluated by TEM, SEM, EDS etc., with the objective of understanding their roles in hepatoma TAE-gene therapy. RESULTS: In vitro, L-nanoplex managed the highest gene transferring efficiency. Though with the second highest transfection activity, Pll-nanoplex showed the strongest tumor inhibition activity while maintaining safe to the normal hepacyte L02. In fact, only Pll-nanoplex can combine both the antitumoral effect to HePG2 and safe procedure to L02 among the four systems above. In vivo, being the only one with successful gene transference to hepatic VX2 tumor, Pll-nanoplex/lipiodol emulsion can target the tumor more specifically, which may explain its best therapeutic effect and hepatic biologic response. Further physical characterizations of the four nanoplexs suggested particle size and proper electronic organic surface may be crucial for nano-TAE gene therapy. CONCLUSION: Pll-nanoplex is the most proper system for the combined therapy due to its selectively retention in liver cancer cells, secondary to its morphological and physico-chemical properties of nanometric particle size, steady emulsion, proper organic and electronic surface.


Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Terapia Genética , Neoplasias Hepáticas/terapia , Proteína Supressora de Tumor p53/genética , Animais , Carcinoma Hepatocelular/diagnóstico , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Emulsões , Óleo Etiodado/administração & dosagem , Feminino , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Nanopartículas , Coelhos , Nanomedicina Teranóstica
18.
BMC Cancer ; 19(1): 938, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601175

RESUMO

BACKGROUND: Intra-arterial therapy with embolics is established for the treatment of malignancies of the liver. However, there are no studies comparing the different effects of various embolics used in clinical practice. Herein, we analyzed the effect of 3 different embolics on tumor growth in a rat model of colorectal liver metastases. METHODS: Eight days after subcapsular implantation of 5 × 105 colorectal cancer cells (CC531) in the left liver lobe of WAG/Rij rats were randomized into 4 groups (n = 8) and underwent intra-arterial hepatic therapy. Animals received either EmboCept S®, DC Bead® or Lipiodol® Ultra-Fluid. Animals of the control group received a comparable amount of saline. Tumor growth was measured on day 8 and 11 using a three-dimensional 40 MHz ultrasound device. On day 11 tumor and liver tissue were removed for histological and immunohistochemical analyses. RESULTS: On day 11 animals of the control group showed a tumor growth of ~ 60% compared to day 8. Application of Lipiodol Ultra-Fluid® did not significantly influence tumor growth (~ 40%). In contrast, treatment with EmboCept S® or DC Bead® completely inhibited tumor growth. Of interest, application of EmboCept S® did not only completely inhibit tumor growth but even decreased tumor size. Immunohistochemical analysis showed a significant increase of necrotic areas within the tumors after application of EmboCept S® and DC Bead® compared to Lipiodol® Ultra-Fluid. CONCLUSION: The present study demonstrates that an intra-arterial therapy with EmboCept S® and DC Bead®, but not Lipiodol® Ultra-Fluid, results in a complete inhibition of rat colorectal liver metastatic growth.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/patologia , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Microesferas , Álcool de Polivinil/uso terapêutico , Amido/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Óleo Etiodado/administração & dosagem , Óleo Etiodado/efeitos adversos , Óleo Etiodado/uso terapêutico , Feminino , Artéria Hepática , Xenoenxertos , Fígado/irrigação sanguínea , Fígado/patologia , Masculino , Modelos Animais , Necrose/patologia , Neovascularização Patológica/tratamento farmacológico , Álcool de Polivinil/administração & dosagem , Álcool de Polivinil/efeitos adversos , Ratos , Amido/administração & dosagem , Amido/efeitos adversos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
19.
J Vasc Interv Radiol ; 30(12): 2026-2035.e2, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590966

RESUMO

PURPOSE: To evaluate the effect of transarterial infusion of iRGD-modified and doxorubicin-loaded zirconia-composite nanoparticles (R-DZCNs) with lipiodol in the improvement of the distribution of doxorubicin (DOX) in liver tumors and its antitumor efficacy. MATERIALS AND METHODS: The effect of R-DZCNs was evaluated in vitro by tumor cellular uptake and cytotoxicity assays. For the in vivo study, DOX distribution and antitumor efficiency were assessed. In the DOX distribution study, VX2 tumor-bearing rabbits received transarterial infusion of lipiodol with DOX, doxorubicin-loaded zirconia-composite nanoparticles (DZCNs), or R-DZCNs, respectively. DOX distribution was assessed by immunofluorescence. In the antitumor study, tumor-bearing rabbits received transarterial infusions of lipiodol with DOX, DZCNs, R-DZCNs, or saline respectively. Tumor volume was measured using magnetic resonance imaging, and the expression of apoptosis-related factors (caspase-3, Bax, Bcl-2) was analyzed by immunohistochemistry and Western blotting. RESULTS: R-DZCNs increased cellular uptake and caused stronger cytotoxicity. Compared with the DOX + lipiodol or DZCNs + lipiodol group, the R-DZCNs + lipiodol group showed more DOX fluorescence spots (2,449.15 ± 444.14 vs. 3,464.73 ± 632.75 or 5,062.25 ± 585.62, respectively; P < .001) and longer penetration distance (117.58 ± 19.36 vs 52.64 ± 8.53 or 83.37 ± 13.76 µm, respectively; P < .001). In the antitumor study, the R-DZCNs + lipiodol group showed smaller tumor volumes than the DOX + lipiodol or DZCNs + lipiodol group (1,223.87 ± 223.58 vs. 3,695.26 ± 666.25 or 2281.06 ± 457.21 mm3, respectively; P = .005).The greatest extent of tumor cell apoptosis was observed in R-DZCNs + lipiodol group immunohistochemistry and Western blotting results. CONCLUSIONS: Transarterial infusion of R-DZCNs with lipiodol improved the distribution of DOX and enhanced its antitumor efficacy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Quimioembolização Terapêutica , Doxorrubicina/administração & dosagem , Portadores de Fármacos , Óleo Etiodado/administração & dosagem , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Nanopartículas Metálicas , Oligopeptídeos/administração & dosagem , Zircônio/administração & dosagem , Animais , Antibióticos Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Células Hep G2 , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Imageamento por Ressonância Magnética , Masculino , Oligopeptídeos/metabolismo , Coelhos , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos , Zircônio/metabolismo
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