RESUMO
A multicenter study was sponsored by the International Atomic Energy Agency (IAEA) to assess the safety and efficacy of transarterial rhenium-188 ((188)Re) HDD lipiodol (radioconjugate to lipiodol using an HDD kit) in the treatment of unresectable hepatocellular carcinoma. During 5 years, 185 patients received at least 1 treatment of radioconjugate, and 51 were retreated. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated after a "scout" dose of radioconjugate. The total injected activity, including the scout dose during the first treatment, ranged from 21 to 364 mCi (mean, 108 mCi/4 GBq). Immediate and late side-effects were minimal. Tumor size could be evaluated in 88 patients. Among these patients, the objective response rate was 25%; stable disease was observed in 53% and tumor progression in 22%. With a median follow-up of 455 days, the estimated 12- and 24-month overall survival was 46% and 23%. This multicenter study shows that (188)Re lipiodol is a safe and cost-effective method to treat primary hepatocellular carcinoma via the transarterial route and requires further evaluation by treatment of greater numbers of patients.
Assuntos
Carcinoma Hepatocelular/radioterapia , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/radioterapia , Radioisótopos/administração & dosagem , Rênio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intra-Arteriais , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Energia Nuclear , Prognóstico , Radioisótopos/uso terapêutico , Planejamento da Radioterapia Assistida por Computador , Rênio/uso terapêuticoRESUMO
OBJECTIVE: To test a new hypothesis that the glue/contrast admixture used for embolisation reduces the dose delivered to AVMs using an experimental model. METHOD: A model was created using a block of "solid water" (6 x 5 x 2 cm) with twelve wells of different depths. Different concentrations of the glue admixture (Enbucrilate + Lipiodol) were used. The model was irradiated using a 5MV beam with a clinical LINAC system and the dose was checked upstream and downstream. Dose was measured using Kodak XV film, a Vidar 16 bit film scanner and software for therapeutic film dosimetry measurements (RIT software). RESULTS: The radiation dose varied with the distance beyond the glue solid water interface. For distances of 0, 2 and 5 mm to the film, the mean reduction was 13.65% (SD = 2.94), 6.87% (SD = 1.95) and 1.75% (SD = 1.14), respectively. There was also correlation with the Lipiodol concentration in the mixture. The maximum reductions for 80, 50 and 20% Lipiodol concentrations were 16.1% (SD = 1.32), 14.85% (SD = 0.98) and 10% (SD = 1.21), respectively. There was no correlation between the glue depth and the dose delivered. CONCLUSION: The hypothesis that the glue mixture used for embolisation reduces the radiation dose delivered was experimentally confirmed with this study.
Assuntos
Malformações Arteriovenosas/terapia , Meios de Contraste/farmacologia , Embolização Terapêutica , Embucrilato/farmacologia , Óleo Iodado/farmacologia , Doses de Radiação , Dosimetria Fotográfica , Humanos , Modelos Cardiovasculares , RadiocirurgiaRESUMO
PURPOSE: Intra-arterial injections (IAI) of 131I-lipiodol is effective in treating hepatocellular carcinoma patients, but is expensive and requires a 7-day hospitalization in a radioprotection room. 188Re is inexpensive, requires no patient isolation, and can be used with lipiodol. METHODS AND MATERIALS: This International Atomic Energy Agency-sponsored phase II trial aimed to assess the safety and the efficacy of a radioconjugate 188Re + lipiodol (188Re-Lip) in a large cohort of hepatocellular carcinoma patients from developing countries. A scout dose is used to determine the maximal tolerated dose (lungs <12 Gy, normal liver <30 Gy, bone marrow <1.5 Gy) and then the delivery of the calculated activity. Efficacy was assessed using response evaluation criteria in solid tumor (RECIST) and alpha-feto-protein (alpha FP) levels and severe adverse events were graded using the Common Toxicity Criteria of the National Cancer Institute scale v2.0. RESULTS: The trial included 185 patients from eight countries. The procedure was feasible in all participating centers. One treatment was given to 134 patients; 42, 8, and 1 received two, three, and four injections, respectively. The injected activity during the first treatment was 100 mCi. Tolerance was excellent. We observed three complete responses and 19 partial responses (22% of evaluable patients, 95% confidence interval 16-35%); 1- and 2-year survivals were 46% and 23%. Some factors affected survival: country of origin, existence of a cirrhosis, Cancer of the Liver Italian Program score, tumor dose, absence of progression, and posttreatment decrease in alpha FP level. CONCLUSIONS: IAI of 188Re-Lip in developing countries is feasible, safe, cost-effective, and deserves a phase III trial.
Assuntos
Carcinoma Hepatocelular/radioterapia , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/radioterapia , Radioisótopos/administração & dosagem , Rênio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Bilirrubina/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Injeções Intra-Arteriais , Óleo Iodado/efeitos adversos , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Radioisótopos/efeitos adversos , Análise de Regressão , Indução de Remissão , Rênio/efeitos adversos , Estatísticas não ParamétricasRESUMO
A multicentre study was sponsored by the International Atomic Energy Agency (Vienna) to assess the safety and efficacy of trans-arterial rhenium-188 HDD conjugated lipiodol (radioconjugate) in the treatment of patients with inoperable hepatocellular carcinoma (HCC). The radioconjugate was prepared by using an HDD (4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) kit developed in Korea, and lipiodol. Over a period of 18 months, 70 patients received at least one treatment of radioconjugate. Some patients were re-treated if there was no evidence of disease progression. The level of radioconjugate administered was based on radiation-absorbed dose to critical normal organs, calculated following a "scout" dose of radioconjugate. The organs at greatest risk for radiation toxicity are the normal liver, the lung and the bone marrow. An Excel spreadsheet was used to determine maximum tolerated activity (MTA), defined as the amount of radioactivity calculated to deliver no more than 12 Gy to lungs, or 30 Gy to liver, or 1.5 Gy to bone marrow. These doses have been found to be safe in multiple trials using external beam therapy, but this has not been confirmed for systemically administered radiopharmaceuticals. Patients were followed for at least 12 weeks after therapy, until recovery from all toxicity. The clinical parameters evaluated included toxicity, response as determined by contrast-enhanced computed tomography, palliation of symptoms, overall survival, performance status (Karnofsky) and hepatic function (Child's classification). Liver function tests, serum alpha-fetoprotein (AFP) levels and complete blood counts were done at each follow-up visit. In the majority of patients, the scout dose studies indicated the radiation absorbed dose to normal liver to be the limiting factor to the treatment dose, while in a few patients dose to lung was the limiting factor. Radiation dose to bone marrow was negligible and was thus not a factor for the MTA calculations. Side-effects were minimal and usually presented as loss of appetite, right hypochondrial discomfort and low-grade fever, even at high levels of administered radioactivity. The symptoms resolved with simple supportive therapy within 3 days of onset. Liver function tests at 24 and 72 h showed no significant changes and complete blood counts at 1 week, 4 weeks and 12 weeks showed no changes (no bone marrow suppression). Sixteen patients were treated in the dose escalation phase of the study, when the activities administered started at 1.8 GBq (50 mCi) and rose to 7.7 GBq (206 mCi). In the efficacy phase of the study a further 54 patients were treated. Both groups of patients are included in this paper. The treatment activity of 188Re-lipiodol administered transarterially ranged from 1.8 to 9.8 GBq (50-265 mCi), with a mean activity of 4.6 GBq (124 mCi). Survival at 3 months was 90%, and at 6 months, 60%; 19% survived for 1 year. Mean survival after treatment in the total treated group of 70 patients was 9.5 months, with a range of 1-18 months. The results of this multicentre study show that 188Re-lipiodol is a safe and cost-effective method to treat primary HCC via the transarterial route. In terms of efficacy, it is potentially a new therapeutic approach for further evaluation by treatment of larger numbers of patients.
Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/radioterapia , Infusões Intra-Arteriais/métodos , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/radioterapia , Rênio/administração & dosagem , Adulto , Idoso , Colômbia/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/etiologia , Feminino , Febre/etiologia , Humanos , Óleo Iodado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Projetos Piloto , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico , Rênio/efeitos adversos , Singapura/epidemiologia , Análise de Sobrevida , Resultado do Tratamento , Vietnã/epidemiologiaAssuntos
Endocrinologia/história , Bócio Endêmico/história , Hipotireoidismo Congênito/história , Deficiências Nutricionais/história , Deficiências Nutricionais/terapia , Equador , História do Século XVIII , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Iodo/uso terapêutico , Óleo Iodado/uso terapêutico , Cloreto de Sódio na Dieta/uso terapêuticoRESUMO
The authors present the angiographic aspects of four patients having an arteriovenous transhepatic transtumoral fistula (two arterioportal and two arteriovenous). The angiographic results of the occlusion with cyanoacrylate (Hystoacryl) of the right hepatic artery in one and by the infusion of Lipiodol in two are also shown. The physiopathological characteristics of each kind of fistula are discussed and the consequences of the passage of the quimioembolizing mixture through the tumor, regarding intrahepatic abscess formation, irregular clinical results and pulmonary complications are commented. These complications make the diagnosis of a transtumoral transhepatic arteriovenous fistula, previously to the chemoembolic treatment important, even though being frequently difficult, because of the reduced caliber of the feeding artery and eventual low transfistular bloodflow. The efficient occlusion of the arterioportal fistula with Histoacryl was favourably compared to the infusion of Lipiodol, which was unable to occlude the arteriovenous fistula. The contraindication to perform chemoembolic treatment of hepatic tumors, when an intrahepatic transtumoral arteriovenous fistula is present and the embolization of the fistular feeding artery is stressed. Ultrasonography using color Doppler and sono-enhancing contrast is appointed as the ideal non-invasive means of making the diagnosis of an hepatic transtumoral fistula and makes it eligible to be the first test in the algorithm for the appraisal of hepatic tumors.
Assuntos
Fístula Arteriovenosa/complicações , Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/complicações , Algoritmos , Angiografia , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Meios de Contraste/administração & dosagem , Cianoacrilatos/administração & dosagem , Feminino , Artéria Hepática/anormalidades , Artéria Hepática/diagnóstico por imagem , Humanos , Óleo Iodado/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Masculino , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagemAssuntos
Humanos , Feminino , Fístula Arteriovenosa , Fístula Arteriovenosa/terapia , Carcinoma Hepatocelular , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas , Neoplasias Hepáticas/terapia , Angiografia , Meios de Contraste/administração & dosagem , Cianoacrilatos/administração & dosagem , Artéria Hepática , Artéria Hepática/anormalidades , Óleo Iodado/administração & dosagem , Veia Porta , Veia Porta/anormalidadesRESUMO
Se presenta una casuística de 211 colocistectomias videocelioscópicas, con propuesta de colangiografía operatoria sistemática, en la que el método fue obviado en 57 casos, frusto en 36 y realizado en 118. El nivel de calidad fue aceptable en sólo 81 estudios. Fueron detectadas 3 litiasis colidocianas, y un paciente con colangiografía operatoria normal mostró vía biliar ocupada meses después. Se concluye en proponer su implementación sistemática
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Colangiografia/história , Colecistectomia , Cálculos Biliares , Laparoscopia , Colangiografia , Colangiografia/efeitos adversos , Colecistectomia/efeitos adversos , Colecistectomia/instrumentação , Cálculos Biliares/diagnóstico , Óleo Iodado , Óleo Iodado/efeitos adversos , Laparoscopia/instrumentação , Laparoscopia/estatística & dados numéricosRESUMO
Se presenta una casuística de 211 colocistectomias videocelioscópicas, con propuesta de colangiografía operatoria sistemática, en la que el método fue obviado en 57 casos, frusto en 36 y realizado en 118. El nivel de calidad fue aceptable en sólo 81 estudios. Fueron detectadas 3 litiasis colidocianas, y un paciente con colangiografía operatoria normal mostró vía biliar ocupada meses después. Se concluye en proponer su implementación sistemática (AU)