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EJNMMI Res ; 11(1): 23, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661428


PURPOSE: To determine which imaging method used during radioembolization (RE) work-up: contrast-enhanced computed tomography (CECT), 99mTc-MAA-SPECT/CT or cone beam-CT (CBCT), more accurately predicts the final target volume (TgV) as well as the influence that each modality has in the dosimetric calculation. METHODS: TgVs from 99mTc-MAA-SPECT/CT, CECT and CBCT were consecutively obtained in 24 patients treated with RE and compared with 90Y PET/CT TgV. Using the TgVs estimated by each imaging modality and a fictitious activity of 1 GBq, the corresponding absorbed doses by tumor and non-tumoral parenchyma were calculated for each patient. The absorbed doses for each modality were compared with the ones obtained using 90Y PET/CT TgV. RESULTS: 99mTc-MAA-SPECT/CT predicted 90Y PET/CT TgV better than CBCT or CECT, even for selective or superselective administrations. Likewise, 99mTc-MAA-SPECT/CT showed dosimetric values more similar to those obtained with 90Y PET/CT. Nevertheless, CBCT provided essential information for RE planning, such as ensuring the total coverage of the tumor and, in cases with more than one feeding artery, splitting the activity according to the volume of tumor perfused by each artery. CONCLUSION: The joint use of 99mTc-MAA-SPECT/CT and CBCT optimizes dosimetric planning for RE procedures, enabling a more accurate personalized approach.

Eur J Nucl Med Mol Imaging ; 48(5): 1570-1584, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33433699


PURPOSE: A multidisciplinary expert panel convened to formulate state-of-the-art recommendations for optimisation of selective internal radiation therapy (SIRT) with yttrium-90 (90Y)-resin microspheres. METHODS: A steering committee of 23 international experts representing all participating specialties formulated recommendations for SIRT with 90Y-resin microspheres activity prescription and post-treatment dosimetry, based on literature searches and the responses to a 61-question survey that was completed by 43 leading experts (including the steering committee members). The survey was validated by the steering committee and completed anonymously. In a face-to-face meeting, the results of the survey were presented and discussed. Recommendations were derived and level of agreement defined (strong agreement ≥ 80%, moderate agreement 50%-79%, no agreement ≤ 49%). RESULTS: Forty-seven recommendations were established, including guidance such as a multidisciplinary team should define treatment strategy and therapeutic intent (strong agreement); 3D imaging with CT and an angiography with cone-beam-CT, if available, and 99mTc-MAA SPECT/CT are recommended for extrahepatic/intrahepatic deposition assessment, treatment field definition and calculation of the 90Y-resin microspheres activity needed (moderate/strong agreement). A personalised approach, using dosimetry (partition model and/or voxel-based) is recommended for activity prescription, when either whole liver or selective, non-ablative or ablative SIRT is planned (strong agreement). A mean absorbed dose to non-tumoural liver of 40 Gy or less is considered safe (strong agreement). A minimum mean target-absorbed dose to tumour of 100-120 Gy is recommended for hepatocellular carcinoma, liver metastatic colorectal cancer and cholangiocarcinoma (moderate/strong agreement). Post-SIRT imaging for treatment verification with 90Y-PET/CT is recommended (strong agreement). Post-SIRT dosimetry is also recommended (strong agreement). CONCLUSION: Practitioners are encouraged to work towards adoption of these recommendations.

Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/radioterapia , Microesferas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Agregado de Albumina Marcado com Tecnécio Tc 99m , Radioisótopos de Ítrio/uso terapêutico
Front Immunol ; 10: 1151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31231366


Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI.

Mol Ther ; 26(11): 2696-2709, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30195725


Diabetes is a chronic metabolic disorder that affects 415 million people worldwide. This pathology is often associated with long-term complications, such as critical limb ischemia (CLI), which increases the risk of limb loss and mortality. Mesenchymal stromal cells (MSCs) represent a promising option for the treatment of diabetes complications. Although MSCs are widely used in autologous cell-based therapy, their effects may be influenced by the constant crosstalk between the graft and the host, which could affect the MSC fate potential. In this context, we previously reported that MSCs derived from diabetic patients with CLI have a defective phenotype that manifests as reduced fibrinolytic activity, thereby enhancing the thrombotic risk and compromising patient safety. Here, we found that MSCs derived from diabetic patients with CLI not only exhibit a prothrombotic profile but also have altered multi-differentiation potential, reduced proliferation, and inhibited migration and homing to sites of inflammation. We further demonstrated that this aberrant cell phenotype is reversed by the platelet-derived growth factor (PDGF) BB, indicating that PDGF signaling is a key regulator of MSC functionality. These findings provide an attractive approach to improve the therapeutic efficacy of MSCs in autologous therapy for diabetic patients.

Diabetes Mellitus/genética , Inflamação/genética , Células-Tronco Mesenquimais/metabolismo , Proteínas Proto-Oncogênicas c-sis/genética , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Terapia Baseada em Transplante de Células e Tecidos/métodos , Células Cultivadas , Complicações do Diabetes/genética , Complicações do Diabetes/patologia , Complicações do Diabetes/terapia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Humanos , Inflamação/patologia , Inflamação/terapia , Camundongos , Camundongos SCID , Osteogênese/genética , Fenótipo , Proteínas Proto-Oncogênicas c-sis/uso terapêutico , Transdução de Sinais , Cicatrização/genética
Diabetes ; 62(12): 4266-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24043757


Stem cells have been successfully used for the treatment of critical limb ischemia (CLI). We conducted a clinical trial to determine the feasibility of using autologous adipose-derived mesenchymal stromal cells (AdMSCs) for the treatment of CLI. Unexpectedly, two diabetic patients developed peripheral microthrombosis. This adverse effect, which contrasts with the reported antithrombotic properties of MSCs, may stem from the diabetic environment that alters the fibrinolytic activity of AdMSCs, thereby increasing the probability of developing thrombosis. Here, we confirm this premise by demonstrating that diabetic AdMSCs cultured in the presence of blood sera expressed and released higher levels of plasminogen activator inhibitor type 1, reduced levels of tissue plasminogen activator, and lower d-dimer formation compared with nondiabetic AdMSCs. Thus, to establish an appropriate cell therapy for diabetic patients, we recommend including new preclinical safety tests, such as the d-dimer and/or the tissue plasminogen activator-to-plasminogen activator inhibitor type 1 ratio tests, to assess fibrinolytic activity of cells before implantation.

Tecido Adiposo/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fibrinólise/fisiologia , Células-Tronco Mesenquimais/fisiologia , Tecido Adiposo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/patologia , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativador de Plasminogênio Tecidual/sangue
Cardiovasc Intervent Radiol ; 33(3): 523-31, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19841973


We evaluated the feasibility, safety, and efficacy of radioembolization (administered from one or two vascular points) after the redistribution of arterial blood flow in the liver in patients with hepatic neoplasms and arterial anatomic peculiarities (AAP). Twenty-four patients with liver neoplasms and AAP (graded according to Michel's classification) were included in the study. During pretreatment angiographic planning, all extrahepatic vessels that could feed the tumor were embolized and the intrahepatic vessels occluded in order to redistribute blood flow. The distribution of microspheres was initially assessed by using technetium-99m-labeled macroaggregated albumin ((99m)Tc-MAA) from one of two vascular points before the administration of yttrium-90 ((90)Y)-radiolabeled resin microspheres. Perfusion of lesions situated in the redistributed segments (L-RS) and nonredistributed segments (L-NRS) were compared by assessing the distribution of (99m)Tc-MAA by SPECT/CT. Perfusion was graded as normal, reduced, or absent. (90)Y resin microspheres were then injected from the same arterial sites as (99m)Tc-MAA and the tumor response recorded 3 months later. The tumor response in L-RS was compared with that in L-NRS and graded as better, similar, or worse. Among 11 patients with type I AAP in whom mainly vessels in segments I-III or IV were occluded, perfusion of L-RS was graded as similar (n = 7) or reduced (n = 4). Among the remaining 13 patients with AAP types III (n = 3), V (n = 4), VIII (n = 3), and others (n = 3) in which aberrant arteries were occluded, perfusion of L-RS was graded as similar (n = 9), reduced (n = 3), or absent (n = 1). Overall, (99m)Tc-MAA was present in the L-RS of 95.8% patients and the distribution of (99m)Tc-MAA in L-RS and L-NRS were graded as similar in 66.6% of patients. Compared with lesions in the L-NRS, tumor response in L-RS was similar in 23 cases and worse in 1 case. No complications were recorded after the administration of (90)Y resin microspheres. Redistribution of flow in L-RS is feasible and enables a safe and effective delivery of (90)Y resin microspheres that are able to be distributed via intrahepatic collaterals and access the microvasculature of L-RS.

Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Radioisótopos de Ítrio/uso terapêutico , Idoso , Angiografia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Microesferas , Pessoa de Meia-Idade , Radiografia Intervencionista , Compostos Radiofarmacêuticos/uso terapêutico , Estudos Retrospectivos , Segurança , Agregado de Albumina Marcado com Tecnécio Tc 99m/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada por Raios X
Cardiovasc Intervent Radiol ; 32(4): 727-36, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19449060


Intra-arterial radiotherapy with yttrium-90 microspheres (radioembolization) is a therapeutic procedure exclusively applied to the liver that allows the direct delivery of high-dose radiation to liver tumors, by means of endovascular catheters, selectively placed within the tumor vasculature. The aim of the study was to describe the distribution of spheres within the precapillaries, inflammatory response, and recannalization characteristics after embolization with nonradioactive resin microspheres in the kidney and liver. We performed a partial embolization of the liver and kidney vessels in nine white pigs. The left renal and left hepatic arteries were catheterized and filled with nonradioactive resin microspheres. Embolization was defined as the initiation of near-stasis of blood flow, rather than total occlusion of the vessels. The hepatic circulation was not isolated so that the effects of reflux of microspheres into stomach could be observed. Animals were sacrificed at 48 h, 4 weeks, and 8 weeks, and tissue samples from the kidney, liver, lung, and stomach evaluated. Microscopic evaluation revealed clusters of 10-30 microspheres (15-30 microm in diameter) in the small vessels of the kidney (the arciform arteries, vasa recti, and glomerular afferent vessels) and liver. Aggregates were associated with focal ischemia and mild vascular wall damage. Occlusion of the small vessels was associated with a mild perivascular inflammatory reaction. After filling of the left hepatic artery with microspheres, there was some evidence of arteriovenous shunting into the lungs, and one case of cholecystitis and one case of marked gastritis and ulceration at the site of arterial occlusion due to the presence of clusters of microspheres. Beyond 48 h, microspheres were progressively integrated into the vascular wall by phagocytosis and the lumen recannalized. Eight-week evaluation found that the perivascular inflammatory reaction was mild. Liver cell damage, bile duct injury, and portal space fibrosis were not observed. In conclusion, resin microspheres (15-30 microm diameter) trigger virtually no inflammatory response in target tissues (liver and kidney). Clusters rather than individual microspheres were associated with a mild to moderate perivascular inflammatory reaction. There was no evidence of either a prolonged inflammatory reaction or fibrosis in the liver parenchyma following recannalization.

Resinas Acrílicas/farmacologia , Embolização Terapêutica/métodos , Rim/irrigação sanguínea , Fígado/irrigação sanguínea , Animais , Materiais Biocompatíveis , Embolização Terapêutica/instrumentação , Inflamação , Microesferas , Modelos Animais , Tamanho da Partícula , Suínos
J Vasc Interv Radiol ; 19(11): 1625-38, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18823795


PURPOSE: To perform a study in a porcine model comparing four different spherical embolic particles in terms of postembolization patency, deformation, and potential for recanalization, with a focus on a relatively new agent--HepaSphere. MATERIALS AND METHODS: Partial embolization of both kidneys was performed in 18 pigs. Nine animals were sacrificed at 48 hours and nine at 4 weeks. In the same animal, the right kidney was embolized with HepaSphere particles ("dry" size, 50-100 microm; presumed final size, 200-300 microm), and the left kidney was alternatively embolized with EmboSphere (100-300 microm), Contour (150-350 microm), or Bead Block (150-350 microm) particles. The authors analyzed the size, deformation, and number of particles in each vessel, their morphologic characteristics, and recanalization. RESULTS: Particle sizes and deformation (1,096 particles) were as follows: HepaSphere, 225.3 microm +/- 67 and 26% +/- 19.7, respectively; EmboSphere, 132.9 microm +/- 36 and 18.1% +/- 14.2; Bead Block, 108.1 microm +/- 38 and 16.5% +/- 13.9; and Contour, 240.8 microm +/- 135 and 55.5% +/- 33. HepaSphere and Bead Block particles were distally located, and EmboSphere and Contour particles were located more proximally. EmboSphere and Bead Block particles were round, HepaSphere particles were round and/or ovoid, and Contour particles had an amorphous aspect. EmboSphere particles had a higher tendency to aggregate. No recanalization was seen with HepaSphere particles, and variable recanalization was observed with the others. CONCLUSIONS: Despite similar initial morphologic characteristics, the performance of the agents tested in this study differed in terms of final size, shape, deformation, and luminal recanalization. These differences have potential clinical relevance, and the knowledge of the differing embolic performance may be helpful in choosing agents for specific therapeutic purposes.

Resinas Acrílicas/administração & dosagem , Embolização Terapêutica/métodos , Hemostáticos/administração & dosagem , Rim/citologia , Rim/efeitos dos fármacos , Animais , Feminino , Humanos , Rim/irrigação sanguínea , Modelos Animais , Tamanho da Partícula , Suínos
Radiología (Madr., Ed. impr.) ; 47(6): 329-334, nov. 2005. ilus, tab
Artigo em Es | IBECS | ID: ibc-041553


Objetivos: Describir la técnica empleada y valorar los resultados, en la implantación percutánea de un catéter en la arteria hepática a través de la subclavia izquierda, para administración de quimioterapia regional. Material y métodos: Entre abril de 1999 y junio de 2002, a 33 pacientes (17 varones y 16 mujeres) de 52,9 años de media y con evidencia de lesión hepática (32 metástasis hepáticas, un hepatocarcinoma fibrolamelar), se les implantaron 36 catéteres intraarteriales. El acceso en todos los casos fue la arteria subclavia izquierda con guía ecográfica. Se estudió la vascularización hepática y se emplazó el catéter distal en arteria hepática. Asimismo, se embolizaron ramas extrahepáticas de la arteria hepática, para evitar fuga del quimioterápico. La cánula se conectó al reservorio (Port-a-cath Titaniumvenous system. Daltec MN. USA) implantado, subcutáneo, próximo al punto de punción. Resultados: El éxito técnico se consiguió en todos los casos (catéter en arteria hepática común en 31 casos, tres en la arteria hepática derecha, uno en la arteria hepática izquierda procedente de la gástrica izquierda y uno en la arteria hepática derecha procedente de la mesentérica superior). La permanencia de los reservorios osciló entre 22 y 740 días (media, 222,4 días). Se registraron complicaciones en 13 casos (36,1%): cinco migraciones de cánula, cuatro vainas de fibrina, tres obstrucciones del vaso cateterizado, una contaminación y una fuga en la conexión. Se solucionaron de modo percutáneo o con retirada del dispositivo. Conclusión: La implantación percutánea de un catéter intraarterial hepático y reservorio, a través de la subclavia izquierda con ayuda ecográfica, es técnicamente factible, y con una tasa de complicaciones aceptable además de solucionables percutáneamente

Objetives: To describe the technique used and to assed about the results obtained in the percutaneous implantation of a catheter in hepatic artery (HA) through left subclavian artery to administer regional chemotherapy. Material and methods: Between April 1999 and June 2002, 33 patients (17 men and 16 women) with a mean age of 52.9 years and with evidence of hepatic lesion (32 hepatic metastases, 1 fibrolamellar hepatocarcinoma (HCC), 36 intra-arterial catheters were implanted. Access in every case was the left subclavian artery with ultrasonographic guide. Hepatic vascularization was studied and distal catheter was located in the HA. Furthermore, extrahepatic branches of the HA were embolized to avoid chemotherapeutic escape. The cannula was connected to the subcutaneous implanted reservoir (Port-a-cath Titaniumvenous system. Daltec. M.N. USA) close to the puncture point. Results: Technical success was achieved in every case (catheter in common HA 31 cases, 3 in right HA, 1 in left HA from left gastric artery and 1 in right HA from upper mesenteric artery). The permanence of the reservoirs ranged from 22 to 740 days (mean 222.4 days). Complications were recorded in 13 cases (36.1%): 5 canula migrations, 4 fibrin sheath, 3 obstruction of catheterized vessel, 12 contamination and 1 escape from the connection. They were solved percutaneously or by withdrawal of the device. Conclusion: Percutaneous implantation of an intra-arterial hepatic catheter and reservoir through the left subclavian artery with ultrasonographic guidance is technically feasible and has an acceptable rate of complications besides being percutaneously solutionable

Masculino , Feminino , Adulto , Idoso , Pessoa de Meia-Idade , Humanos , Cateterismo/métodos , Cateteres de Demora , Tratamento Farmacológico/métodos , Artéria Hepática , Artéria Subclávia , Bombas de Infusão Implantáveis , Resultado do Tratamento
Radiología (Madr., Ed. impr.) ; 47(3): 119-128, mayo 2005.
Artigo em Es | IBECS | ID: ibc-040111


En pacientes con tumores hepáticos, el tratamiento más eficaz es la cirugía. Sin embargo, no todos pueden ser tratados de esta manera. Uno de los motivos que contraindican el tratamiento quirúrgico es que el parénquima hepático que queda tras la resección de la zona tumoral sea insuficiente para asegurar la función hepática del paciente. Es conocido que el hepatocito, tras determinados estímulos, tiene la posibilidad de desdiferenciarse y clonarse. La embolización portal prequirúrgica (EPP) del volumen hepático que se va a resecar puede generar, tras este estímulo y respuesta (que será diferente en hígados fibróticos y no fibróticos), un crecimiento hepático que alcanzará niveles adecuados en 3-4 semanas. Por tanto, la EPP puede incrementar el número de candidatos a recibir tratamiento quirúrgico y, del mismo modo, puede disminuir la aparición de posibles complicaciones postoperatorias. En este artículo se presentan lo criterios de inclusión y exclusión que, de forma comúnmente aceptada, se utilizan para realizar una EPP. No hay acuerdo, sin embargo, sobre la técnica más adecuada para acceder al sistema portal, por ejemplo, la vía contralateral (con punción de los segmentos portales que no van a ser resecados) tiene considerables ventajas técnicas, pero pone en riesgo de trombosis a las ramas portales del tejido hepático sano. Son muchos los materiales embolizantes que se han usado en EPP, algunos autores recomiendan el empleo de «pegamentos», pues son relativamente sencillos de utilizar, de bajo coste y altamente eficaces pero, por otra parte, generan una importante inflamación periportal que puede dificultar la resección quirúrgica. Si se emplean partículas, éstas deben ser de un tamaño que oscile entre las 100 y las 300 micras. En conclusión, aunque todavía hay muchos aspectos de la EPP que requieren ser investigados, la técnica debería de estar disponible en todos los centros en los que se realice cirugía hepática, pues los beneficios clínicos derivados de ésta son muy satisfactorios

Surgery is the most efficacious treatment for hepatic tumors; however, not all patients with hepatic tumors can be treated surgically. One condition in which surgery is contraindicated is when the amount of liver parenchyma remaining after resection of the affected zone is considered to be insufficient to ensure hepatic function. The hepatocyte is known to be able to dedifferentiate and clone itself after certain stimuli. Presurgical portal embolization (PPE) of the hepatic volume to be resected can generate hepatic growth after this stimulus and response (which will be different in fibrotic and nonfibrotic livers), achieving adequate levels within 3-4 weeks. Therefore, PPE can increase the number of candidates for surgical treatment and decrease the number of possible postsurgical complications. This article describes the commonly accepted inclusion and exclusion criteria used for PPE. There is no consensus, however, regarding the most appropriate technique for accessing the portal system. For example, the contralateral approach (with puncture of the portal segments that are not to be resected) has considerable technical advantages, but places the portal branches of healthy liver tissue at risk for thrombosis. Many different materials have been used for embolization in PPE. Some authors recommend the use of "glues", as these are relatively easy to use, low cost, and highly efficacious; however, they also generate significant periportal inflammation that can make surgical resection more difficult. If particles are used, they should measure between 100-300 micras. In conclusion, although many aspects of PPE still need to be investigated, this technique should be made available in all centers performing hepatic surgery, as it can result in significant clinical benefits

Humanos , Cuidados Pré-Operatórios/métodos , Embolização Terapêutica/métodos , Veia Porta/cirurgia , Neoplasias Hepáticas/cirurgia , Transtornos da Coagulação Sanguínea/complicações , Embolização Terapêutica , Tomografia Computadorizada por Raios X