RESUMO
This study aims to evaluate the efficacy and safety of a neoadjuvant treatment protocol with repeated transarterial chemoembolization (TACE) before MR-guided laser-induced thermotherapy (LITT) for large-sized hepatocellular carcinomas (HCC). Repeated TACE (mean, 3.5 treatments per patient) was performed in 48 patients with neoadjuvant intention (the largest lesion was between 50 and 80 mm in diameter, and there were no more than five lesions). For the TACE treatment, we used 10 mg/m(2) mitomycin, 10 ml/m(2) Lipiodol and microspheres. The tumor volume was measured by MRI. Lipiodol retention of the tumors was evaluated with CT. After the diameter of the tumors had decreased to less than 50 mm, the patients were treated with MR-guided LITT 4 to 6 weeks after embolization. Repeated TACE reduced the tumor size in 32 patients (66.7%), forming the basis for performing MR-guided LITT procedures. These patients received one to four laser treatments (mean, 1.9 per patient) for tumor ablation, resulting in a median survival of 36.0 months after the first treatment. For the remaining patients, no reduction in tumor size was achieved in 12 patients and disease progression in 4 patients. Neoadjuvant TACE appears to be an effective treatment of large-sized HCC, which extends the indication for MR-guided LITT.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hipertermia Induzida , Lasers , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Terapia Neoadjuvante , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Ablação por Cateter , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Meios de Contraste , Imagem Ecoplanar , Feminino , Seguimentos , Humanos , Hipertermia Induzida/efeitos adversos , Hipertermia Induzida/métodos , Óleo Iodado , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Imageamento por Ressonância Magnética/métodos , Masculino , Microesferas , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
Chronic lung hypoxia causes vascular remodeling with pulmonary artery smooth muscle cell (SMCPA) hyperplasia, resulting in pulmonary hypertension and cor pulmonale. We investigated SMCPA and pulmonary artery adventitial fibroblasts (FBPA) for their proliferative response to hypoxia. Strong SMCPA growth occurred under hypoxic conditions in SMCPA/FBPA co-cultures, but not in SMCPA monocultures. SMCPA growth was fully reproduced by transferring serum-free supernatant from hypoxic cultured FBPA to normoxic SMCPA. Hypoxia-inducible-transcription-factor subtypes (HIF-1alpha, HIF-2alpha, HIF-3alpha) and its dependent target genes, carrying the hypoxia-responsive-element as regulatory component, were strongly activated in both hypoxic FBPA and SMCPA. HIF-transcription-factor decoy technique, employed to FBPA during hypoxic culturing, blocked the mitogenic activity of FBPA conditioned medium on SMCPA. The data suggest that hypoxia-driven gene regulation in pulmonary artery fibroblasts results in a mitogenic stimulus on adjacent pulmonary artery smooth muscle cells, and HIF-transcription-decoy may offer a new therapeutic approach to suppress these events.
