RESUMO
BACKGROUND AND AIMS: Conventional transcatheter arterial chemoembolization (C-TACE) and drug-eluting bead (DEB)-based TACE are current treatments for hepatocellular carcinoma (HCC). We compared the therapeutic efficacies and adverse events of these methods in a single-center retrospective cohort study. METHODS: We enrolled 174 patients treated between January 2010 and October 2016; 98 and 76 underwent C-TACE and DEB-TACE, respectively, with 76 and 22 of the former group and 49 and 27 of the latter group classified as Child-Pugh class A and B, respectively. Therapeutic outcomes, progression-free survival (PFS), and adverse events were evaluated. RESULTS: The PFS rates in the C-TACE and DEB-TACE groups were 8.1 and 6.1 months, respectively (p = 0.79). The response and disease control rates were 64 and 71% in C-TACE patients and 69 and 78% in DEB-TACE patients, respectively (p = 0.25). Postprocedural pain, vomiting, and fever were more frequent following C-TACE than DEB-TACE (p < 0.001). In contrast, the incidences of bilomas and arterio-portal shunts were significantly higher following DEB-TACE (p < 0.001); the incident rates of arterio-portal shunt formation were 8.1 and 48.7% in patients undergoing C-TACE and DEB-TACE, respectively. Child-Pugh class A was significantly associated with arterio-portal shunt formation after DEB-TACE on multivariate analysis. CONCLUSIONS: There were no significant differences in the therapeutic efficacies of C-TACE and DEB-TACE. However, the frequency of arterio-portal shunt formation was significantly higher in HCC patients with Child-Pugh class A undergoing DEB-TACE. Our findings imply that C-TACE should be selected for HCC patients with Child-Pugh class A and DEB-TACE should be chosen for those with Child-Pugh class B.
Assuntos
Fístula Arteriovenosa/etiologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Sistemas de Liberação de Medicamentos/efeitos adversos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/terapia , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Cateterismo/métodos , Epirubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
AIM: Prognosis of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) is extremely poor. However, proper therapeutic strategies have not been established yet. The purpose of this study is to identify the effects of external beam radiation therapy (EBRT) for MVI of HCC. METHODS: We have analyzed and evaluated 80 consecutive patients with HCC with MVI who underwent EBRT, and factors associated with enhanced survival in EBRT were evaluated by univariate and multivariate analysis. RESULTS: The local response rate of radiotherapy for the irradiated MVI was 66.2%. The time to progression of the irradiated MVI was 5.8 months. Univariate and multivariate analyses showed that the higher irradiation dose (over 45 Gy) and the irradiation location (hepatic vein tumor thrombus - HVTT) were significant factors associated with survival benefits of EBRT. The response of EBRT for HVTT was significantly superior to that for portal vein or bile duct tumor thrombus. CONCLUSION: We conclude that a multidisciplinary therapeutic strategy based on EBRT should be proactively selected in the treatment of advanced HCC with MVI.
Assuntos
Ductos Biliares Intra-Hepáticos/efeitos da radiação , Carcinoma Hepatocelular/radioterapia , Veias Hepáticas/efeitos da radiação , Neoplasias Hepáticas/radioterapia , Veia Porta/efeitos da radiação , Dosagem Radioterapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares Intra-Hepáticos/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Veias Hepáticas/diagnóstico por imagem , Veias Hepáticas/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Transcatheter arterial chemoembolization (TACE) is a standard therapy used in the treatment of intermediate hepatocellular carcinoma (HCC). Recently, balloon-occluded TACE (B-TACE) has been developed. PURPOSE: This study aimed to clarify the effects of B-TACE in patients with HCC, with a focus on which drug is suitable to suspend in Lipiodol for B-TACE. METHODS: We retrospectively evaluated 35 patients with HCC treated with B-TACE. Factors associated with enhanced time to progression (TTP) after B-TACE were evaluated using univariate and multivariate analyses. RESULTS: A total of 35 patients with HCC (40 nodules) were treated with B-TACE between June 2013 and August 2016. Epirubicin was used in 25 nodules and miriplatin was used in 15 nodules. Epirubicin (15.1 months) was significantly better than miriplatin (3.2 months) in prolonging the local TTP after B-TACE (p = 0.0293). Epirubicin showed a positive tendency in TE4 (100% tumor necrosis) rate when compared with miriplatin (p = 0.058). Achievement of TE4 was the only significant factor associated with better TTP after B-TACE. Epirubicin- and TACE-naïve statuses were significant factors in achieving TE4 with B-TACE. CONCLUSION: To enhance the TTP with B-TACE, TE4 should be achieved. Epirubicin is a more optimal anticancer drug (as a Lipiodol suspension) than miriplatin for achieving TE4 with B-TACE.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Epirubicina/administração & dosagem , Neoplasias Hepáticas/terapia , Compostos Organoplatínicos/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Óleo Etiodado/administração & dosagem , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Orexins (also called hypocretins), which are neuropeptides exclusively expressed by a population of neurons specifically localized in the lateral hypothalamic area, are critically implicated in the regulation of sleep/wake states. Orexin deficiency results in narcoleptic phenotype in rodents, dogs, and humans, suggesting that orexins are important for maintaining consolidated wakefulness states. However, the physiological effect of constitutive increased orexinergic transmission tone, which might be important for understanding the effects of orexin agonists that are promising candidates for therapeutic agents of narcolepsy, has not been fully characterized. We report here the sleep/wakefulness abnormalities in transgenic mice that exhibit widespread overexpression of a rat prepro-orexin transgene driven by a ß-actin/cytomegalovirus hybrid promoter (CAG/orexin transgenic mice). CAG/orexin mice exhibit sleep abnormalities with fragmentation of non-rapid eye movement (REM) sleep episode and a reduction in REM sleep. Non-REM sleep was frequently disturbed by short episodes of wakefulness. EEG/EMG studies also reveal incomplete REM sleep atonia with abnormal myoclonic activity during this sleep stage. These results suggest that endogenous orexinergic activity should be appropriately regulated for normal maintenance of sleep states. Orexinergic transmission should be activated during wakefulness, while it should be inactivated or decreased during sleep state to maintain appropriate vigilance states.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Tono Muscular/fisiologia , Neuropeptídeos/metabolismo , Sono REM/fisiologia , Vigília/fisiologia , Animais , Eletroencefalografia , Eletromiografia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Transgênicos , Neuropeptídeos/genética , Orexinas , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , RatosRESUMO
Hypothalamic neurons that contain the neuropeptide orexin (hypocretin) play important roles in the regulation of sleep/wake. Here we analyze the in vivo and in vitro phenotype of mice lacking the GABA(B1) gene specifically in orexin neurons (oxGKO mice) and demonstrate that GABA(B) receptors on orexin neurons are essential in stabilizing and consolidating sleep/wake states. In oxGKO brain slices, we show that the absence of GABA(B) receptors decreases the sensitivity of orexin neurons to both excitatory and inhibitory inputs because of augmented GABA(A)-mediated inhibition that increases the membrane conductance and shunts postsynaptic currents in these neurons. This increase in GABA(A)-mediated inhibitory tone is apparently the result of an orexin receptor type 1-mediated activation of local GABAergic interneurons that project back onto orexin neurons. oxGKO mice exhibit severe fragmentation of sleep/wake states during both the light and dark periods, without showing an abnormality in total sleep time or signs of cataplexy. Thus, GABA(B) receptors on orexin neurons are crucial in the appropriate control of the orexinergic tone through sleep/wake states, thereby stabilizing the state switching mechanisms.