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1.
Vasc Endovascular Surg ; 54(2): 135-140, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31769352

RESUMO

PURPOSE: Ultrasound-facilitated, catheter-directed, low-dose fibrinolysis (USAT) appears to provide promising results for the management of acute submassive pulmonary embolisms (ASMPEs) at tertiary care centers. This study assessed outcome measures at a community-based hospital systems and compared results to known studies. MATERIALS AND METHODS: This is a single-center, retrospective study assessing clinical outcomes of the EkoSonic Endovascular System intervention for ASMPEs performed by three surgical 3 subspecialties (interventional radiology, interventional cardiology, and vascular surgery) part of a pulmonary embolism response team (PERT). We reviewed 146 PERT activations from June 2013 to December 2017. Eighty-three patients with ASMPEs underwent USAT. RESULTS: Our study showed greater differences (P = .01) between baseline and follow-up pulmonary artery systolic pressures (20.9 ± 9.8 mm Hg [n = 14]) compared to the ULTIMA study (12.3 ± 10 mm Hg [n = 30]). Our length-of-stay measures were shorter (6.1 ± 5.1 [n = 83]; P = .0001) compared to the SEATTLE II study (8.8 ± 5.0 [n = 150]). Preprocedure transthoracic echocardiograms (TTEs) were performed for 54 (65%) of 83 patients. Postprocedure TTEs at 48 hours was performed for 52 (62%) of 83 patients. Use of TTEs before and after intervention did not change outcomes. Intracranial hemorrhage was not observed in our patient population. There was no difference in outcomes between the three subspecialties in our study. CONCLUSIONS: Use of USAT in a community-based hospital PERT has similar outcomes to tertiary care centers. Furthermore, similar outcomes were observed between the three subspecialties suggesting development of a comprehensive care team for management of ASMPEs.


Assuntos
Cateterismo Periférico , Fibrinolíticos/administração & dosagem , Hospitais Comunitários , Embolia Pulmonar/terapia , Terapia Trombolítica/métodos , Terapia por Ultrassom , Doença Aguda , Adulto , Idoso , Cardiologistas , Cateterismo Periférico/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intra-Arteriais , Masculino , Michigan , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/fisiopatologia , Radiologistas , Estudos Retrospectivos , Especialização , Cirurgiões , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Terapia por Ultrassom/efeitos adversos
2.
Int J Cancer ; 146(7): 2019-2026, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31872440

RESUMO

In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Imunidade/efeitos dos fármacos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Oxaliplatina/administração & dosagem , Adulto , Idoso , Biomarcadores , Ablação por Cateter , Neoplasias Colorretais/metabolismo , Terapia Combinada , Feminino , Seguimentos , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/terapia , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(51): e18516, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861039

RESUMO

BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) is the most common bladder cancer. Many studies have reported that intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) could effectively reduce the recurrence rate of NMIBC. The purpose of this study is to assess the efficacy and safety of IAC combined with IVC for patients with high-risk NMIBC. METHODS: PubMed, Cochrane Library, Medline, Embase, Web of Science, and 4 Chinese databases will be searched for eligible studies published without language restrictions from their inception up August 31, 2019. Subgroup analysis will be mainly explored in study design, types of chemotherapy drugs, and sample size. Cochrane Collaboration Risk of bias Tool will be applied in evaluating the quality of enrolled articles. Statistical analysis will be carried out by the Stata version 14.0 software. RESULTS: The primary outcome is recurrence-free survival (RFS). The secondary outcomes include overall survival (OS), progression-free survival (PFS), adverse reactions and toxicity grade coded by common toxicity criteria for adverse events. CONCLUSION: The findings of this study will provide latest evidence to verify whether IAC combined with IVC is more effective and safer than IVC alone for patients with high-risk NMIBC. PROSPERO REGISTRATION NUMBER: CRD42019146847.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Humanos , Infusões Intra-Arteriais , Metanálise como Assunto , Revisão Sistemática como Assunto
4.
Clin Nucl Med ; 44(12): 989-990, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31663867

RESUMO

Nasopharyngeal carcinoma may express somatostatin receptors (SSTR). We present a case with metastatic nasopharyngeal carcinoma in the liver, bone, and lymph nodes. The patient was in progression after chemotherapy, external beam radiation therapy (ERBT), atezolizumab, and cetuximab. Due to strong SSTR expression of the metastases, PRRT was applied. After 3 cycles of intravenous Lu-DOTATOC and 1 cycle of intraarterial Y-DOTATOC therapy, the hepatic and bone metastases showed excellent response after PRRT. No nephrotoxicity or myelotoxicity was observed.


Assuntos
Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/radioterapia , Octreotida/análogos & derivados , Receptores de Peptídeos/metabolismo , Administração Intravenosa , Adulto , Humanos , Infusões Intra-Arteriais , Masculino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Metástase Neoplásica , Octreotida/administração & dosagem , Octreotida/uso terapêutico , Resultado do Tratamento
5.
BMC Cancer ; 19(1): 954, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615466

RESUMO

BACKGROUND: The efficacy of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) remains unclear. We conducted a multi-center randomized phase II study comparing a sequential HAIC-sorafenib regimen versus sorafenib alone as an initial therapy for HCC. METHODS: Patients were randomly assigned (ratio, 1:1) to receive sequential HAIC with cisplatin followed by sorafenib (HAIC group, n = 35) or sorafenib alone (sorafenib group, n = 33) as an initial therapy. The primary endpoint was the one-year survival rate. Secondary endpoint included overall survival (OS), the 2-year survival rate, the time-to-progression (TTP), the objective response rate (ORR), the disease control rate (DCR), and safety. RESULTS: For the primary endpoint, the one-year survival rates were 46% in the HAIC group and 58% in the sorafenib group. The median OS period was 10.0 months (95% CI, 7.0-18.8) in the HAIC group and 15.2 months (95% CI, 8.2-19.7) in the sorafenib group (hazard ratio [HR], 1.08; 95% CI, 0.63 to 1.86, P = 0.78). The median TTP, ORR and DCR in the HAIC group were 2.8 months (95% CI, 1.7-5.5), 14.3, and 45.7%, respectively, while those in the sorafenib group were 3.9 months (95% CI, 2.3-6.8), 9.1, and 45.5%, respectively. No unexpected adverse events related to HAIC or sorafenib were observed in either group. CONCLUSIONS: Sequential HAIC with cisplatin and sorafenib does not improve the survival benefit, compared with sorafenib alone, when used as an initial therapy for advanced HCC. However, this study was underpowered in regard to its primary and secondary endpoints, so the results should be interpreted with caution. TRIAL REGISTRATION: UMIN ID 000006147 , registration data: August 11, 2011.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/uso terapêutico , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Seguimentos , Artéria Hepática , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
6.
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
7.
J Cancer Res Clin Oncol ; 145(11): 2855-2862, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506738

RESUMO

PURPOSE: The treatment of pancreatic carcinoma remains a challenge as prognosis is poor, even if confined to a single anatomical region. A regional treatment of pancreatic cancer with high drug concentrations at the tumor site may increase response behaviour. Intra-arterial administration of drugs generates homogenous drug distribution throughout the entire tumor volume. METHODS: We report on treatment outcome of 454 patients with advanced pancreatic carcinoma (WHO stage III: 174 patients, WHO stage IV: 280 patients). Patients have been separated to two different treatment protocols. The first group (n = 233 patients) has been treated via angiographically placed celiac axis catheters. The second group (n = 221 patients) had upper abdominal perfusion (UAP) with stopflow balloon catheters in aorta and vena cava. Both groups have been treated with a combination of cisplatin, adriamycin and mitomycin. RESULTS: For stage III pancreatic cancer, median survival rates of 8 and 12 months were reached with IA and UAP treatment, respectively. For stage IV pancreatic cancer, median survival rates of 7 and 8.5 months were reached with IA and UAP treatment, respectively. Resolution of ascites has been reached in all cases by UAP treatment. Toxicity was generally mild, WHO grade I or II, toxicity grade III or IV was only noted in patients with severe systemic pretreatment. The techniques, survival data and detailed results are demonstrated. CONCLUSIONS: Responsiveness of pancreatic cancer to regional chemotherapy is drug exposure dependent. The isolated perfusion procedure is superior to intra-arterial infusion in survival times.


Assuntos
Abdome/irrigação sanguínea , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Infusões Intra-Arteriais/mortalidade , Neoplasias Pancreáticas/mortalidade , Abdome/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
8.
Mol Med Rep ; 20(4): 3942-3950, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485662

RESUMO

Intracarotid cold saline infusion (ICSI) brings about neuroprotective effects in ischemic stroke. However, the involvement of serum and glucocorticoid­regulated kinase 1 (SGK1) in the underlying mechanism of ICSI is not fully understood; therefore, we used the rat middle cerebral artery occlusion (MCAO) model to investigate the neuroprotective effects of ICSI on ischemic stroke in rats, as well as the involvement of SGK1 in these effects. ICSI decreased infarct size and brain swelling, as determined by 2,3,5­triphenyltetrazolium chloride staining and the dry­wet weight method, respectively. The results of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and Nissl staining showed that ICSI also suppressed apoptosis and increased the relative integral optical density (IOD) values of Nissl bodies in the rat MCAO model. Regarding the mechanism, the results of immunohistochemistry and western blotting revealed that ICSI upregulated SGK1 expression and downregulated beclin­1 and LC­3 expression in the rat MCAO model. In addition, SGK1 knockdown increased ICSI­mediated infarct size and brain swelling, promoted apoptosis, and reduced the IOD values of Nissl bodies in the rat MCAO model. In addition, we found that SGK1 knockdown upregulated beclin­1 and LC­3 expression mediated by ICSI. Overall, ICSI had a neuroprotective effect on ischemic stroke after reperfusion by upregulating SGK1 and inhibiting autophagy.


Assuntos
Proteínas Imediatamente Precoces/genética , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Proteínas Serina-Treonina Quinases/genética , Solução Salina/uso terapêutico , Regulação para Cima/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/tratamento farmacológico , Edema Encefálico/genética , Edema Encefálico/patologia , Temperatura Baixa , Proteínas Imediatamente Precoces/análise , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/patologia , Infusões Intra-Arteriais , Masculino , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Proteínas Serina-Treonina Quinases/análise , Interferência de RNA , Ratos , Ratos Sprague-Dawley , Solução Salina/administração & dosagem
9.
Cardiovasc Intervent Radiol ; 42(12): 1777-1785, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392490

RESUMO

PURPOSE: Contrast-induced nephropathy (CIN) is one of the leading causes of hospital-acquired acute kidney injury due to the use of iodinated contrast media in various interventional procedures like endovascular aneurysm repair. Its pathophysiology remains mostly unclear. The purpose of the present study was to comparatively study the possible protective role of direct intra-arterial administration of mannitol and acetylcysteine and per os administration of simvastatin in a histopathological level. MATERIALS AND METHODS: In the present study, we administered iopromide directly in the infrarenal aorta of 24 New Zealand white rabbits after laparotomy. Animals were divided in four groups of six: G1 received iopromide with no protection, G2 iopromide with mannitol, G3 iopromide with acetylcysteine, and G4 iopromide with simvastatin. Renal function blood parameters were assessed prior to the administration, and in 48 h; histopathological evaluation of the kidneys was performed. RESULTS: CIN was evident only in the no protection group G1. Moreover, G1 demonstrated significantly more severe lesions than groups G2, G3, and G4 regarding histopathological findings in glomeruli, vacuolization of tubular epithelial cells, tubular proteinaceous casts, and tubular necrosis. According to our results, intra-arterial administration of mannitol seems to be effective in protection against tubular necrosis. CONCLUSION: In general, all three agents demonstrated a protective role in preventing the development of CIN, although it seems that there are various pathways that remain to be investigated further.


Assuntos
Acetilcisteína/uso terapêutico , Lesão Renal Aguda/tratamento farmacológico , Meios de Contraste/efeitos adversos , Manitol/uso terapêutico , Sinvastatina/farmacologia , Acetilcisteína/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Administração Oral , Animais , Modelos Animais de Doenças , Diuréticos Osmóticos/administração & dosagem , Diuréticos Osmóticos/uso terapêutico , Humanos , Infusões Intra-Arteriais , Iohexol/efeitos adversos , Iohexol/análogos & derivados , Masculino , Manitol/administração & dosagem , Coelhos
10.
World J Surg Oncol ; 17(1): 143, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31416447

RESUMO

BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) have a poor oncologic outcome. In this study, we evaluated the role and limitation of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients with Child-Pugh class A and the efficacy of liver resection subsequent to downstaging after neoadjuvant HAIC. METHODS: In the present retrospective study, 103 patients with advanced HCC, who underwent neoadjuvant HAIC from April 2003 to March 2015 were analyzed. Response to HAIC was evaluated by dividing time period into after 3 cycles and after 6 cycles, each defined as early and late period. Liver resection after neoadjuvant HAIC was offered in patients who were considered as possible candidates for curative resection with tumor-free margin as well as sufficient future liver remnant volume. RESULTS: The median survival time (MST) in all patients was 14 ± 1.7 months. Response rate and disease control rate were 36.3% (37) and 81.4% (83) in early period, respectively, and 26.4% (14) and 47.2% (25), in late period, respectively (P = 0.028). Twelve patients (11.7%) underwent liver resection after neoadjuvant HAIC and the MST was 37 ± 6.6 months. One-, 3-, and 5-year recurrence-free survival after liver resection were 58.3%, 36.5%, and 24.3% respectively. Liver resection was identified as the only independent prognostic factor that associated with overall survival in multivariate analysis (P = 0.002) CONCLUSION: HAIC could be further alternative for the treatment of advanced HCC in patients with good liver function. If liver resection is possible after neoadjuvant HAIC, liver resection would provide better outcomes than HAIC alone.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatectomia/mortalidade , Artéria Hepática , Infusões Intra-Arteriais/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Terapia Neoadjuvante/mortalidade , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Cisplatino/administração & dosagem , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Clin Neurosci ; 69: 289-291, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31431407

RESUMO

Mechanical thrombectomy is now at the forefront of the treatment of large vessel acute ischemic stroke (AIS). Selective intra-arterial (IA) access has opened a new avenue for neuroprotection in AIS that has the potential to maximize local benefit while minimizing systemic effects. On a cellular level, neuroprotective strategies are aimed at reducing inflammation and free-radical formation, maintaining blood-brain barrier fidelity, and preventing cellular death. Strategies under investigation include IA infusion of neuroprotective agents, IA administration of stem cells, and selective IA hypothermia. In this technical report, we briefly discuss pathologic mechanisms in AIS and highlight potential neuroprotective strategies that are administered selectively via the IA route.


Assuntos
Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/tendências , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/terapia , Animais , Isquemia Encefálica/terapia , Fibrinolíticos/administração & dosagem , Humanos , Infusões Intra-Arteriais , Trombectomia/métodos
12.
Cardiovasc Intervent Radiol ; 42(10): 1494-1499, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31363899

RESUMO

INTRODUCTION: Significant intratumoral shunts between tumor-supplying arteries and portal or liver veins are a contraindication for transarterial therapy of HCC because interventional treatment of these shunts is frequently insufficient. Sorafenib has anti-angiogenic effects and is indicated for palliative treatment of patients with HCC. Here, we report our experience with the use of sorafenib for the closure of intratumoral shunts in patients scheduled for transarterial therapy of HCC. MATERIALS AND METHODS: Three patients with HCC, aged 65, 82 and 79 years, exhibited a significant intratumoral shunting from tumor artery to portal (n = 1) or liver veins (n = 2). In all cases, intratumoral shunting had already been suspected based on pre-interventional CT angiography, and DSA confirmed the shunt. Oral sorafenib (800 mg/day) was administered for at least four weeks, only and specifically to occlude the shunt. Hereafter, patients were re-evaluated by CT and DSA. RESULTS: All patients tolerated the full prescribed dose for at least 4 weeks. In one case, therapy was prolonged with an adapted dose (400 mg/day) due to sorafenib-related hand-foot syndrome. After sorafenib treatment, CT and DSA confirmed a complete closure of intratumoral shunts for all patients. No tumor progression was observed. All three patients hereafter underwent successful transarterial treatment by TACE (n = 2) or TARE (n = 1) without complications. Progression-free survival according to mRECIST was 501, 397 and 599 days, respectively. CONCLUSION: Even short-term oral sorafenib seems to effectively close intratumoral shunts in patients with HCC and thus might enable transarterial treatment of these patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/irrigação sanguínea , Neoplasias Hepáticas/irrigação sanguínea , Neovascularização Patológica/tratamento farmacológico , Sorafenibe/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Quimioembolização Terapêutica , Feminino , Humanos , Infusões Intra-Arteriais , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Neovascularização Patológica/complicações , Neovascularização Patológica/diagnóstico por imagem , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Anatol J Cardiol ; 22(2): 54-59, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31375648

RESUMO

Catheter-directed intra-arterial thrombolysis (CDT) is a rational treatment method in patients with acute/subacute and even some chronic occlusions of lower extremity arteries and bypass grafts having salvageable limb ischemia. Immediate vessel patency can be achieved with an acceptable complication rate in many patients, especially those with fresh thrombus or emboli. It can be also an adjuvant treatment modality for endovascular interventions for chronic occlusions. There is no standard method of CDT including thrombolytic agent dose and technique. Selection of treatment strategy should be based on individual judgment based on viability of limb, lesion characteristics, and risks of hemorrhage.


Assuntos
Arteriopatias Oclusivas/terapia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Terapia Trombolítica/métodos , Fibrinolíticos/administração & dosagem , Heparina/administração & dosagem , Humanos , Infusões Intra-Arteriais , Proteínas Recombinantes/uso terapêutico , Terapia Trombolítica/instrumentação , Trombose/terapia , Ativador de Plasminogênio Tecidual/uso terapêutico , Dispositivos de Acesso Vascular
14.
J Cancer Res Clin Oncol ; 145(9): 2357-2363, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273511

RESUMO

BACKGROUND: Hepatic arterial infusion (HAI) of chemotherapy could be used in patients with liver-only metastatic colorectal cancer (mCRC) to fight against chemoresistance. We previously reported the efficacy of raltitrexed plus oxaliplatin (HAI) in a retrospective series. We performed a randomized two-stage phase-II study to evaluate the efficacy of HAI of the combination of raltitrexed and oxaliplatin in refractory mCRC with only liver metastases in comparison with standard of care. PATIENTS AND METHODS: Eligible patients had unresectable mCRC and were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type KRAS). Patients were randomized between HAI raltitrexed (3 mg/m2 over 1 h) followed by oxaliplatin (130 mg/m2 over 2 h) every 3 weeks and standard of care in a 2:1 ratio. A total of 57 patients (38 in the experimental arm and 19 in the standard of care arm) were to be included. The main objective was to demonstrate 6-month PFS of 45% by intention-to-treat analysis in the experimental arm, compared to theoretical PFS of 20%, with a unilateral alpha risk of 5% and beta risk of 10%. RESULTS: After inclusion of 27 patients, the trial was terminated due to insufficient accrual. In the experimental arm, 11 and 4 patients experienced grade 3 and 4 toxicities, respectively. The most frequent grade 3-4 toxicities were neutropenia, liver toxicity, and abdominal pain. Median progression-free survival was 6.7 months (95% Confidence Interval; 3.9-7.2) in the HAI group and 2.2 months (95% CI 1.2-4.3) with standard of care [HR 0.32 (95% CI 0.14-0.76), p = 0.01]. Median overall survival did not differ between the two groups, at 11.2 months (95% CI 4.8-17.6) for the HAI group and 11.9 months (95% CI 2.8-14.3) for standard of care [HR 0.86 (95% CI 0.36-2.04), p = 0.73]. CONCLUSION: Although stopped prematurely, this randomized trial provides evidence for the benefit and safety of HAI of a combination of raltitrexed and oxaliplatin in liver-only mCRC with chemoresistant disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Oxaliplatina/administração & dosagem , Quinazolinas/administração & dosagem , Tiofenos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , França , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Oxaliplatina/efeitos adversos , Quinazolinas/efeitos adversos , Padrão de Cuidado , Tiofenos/efeitos adversos , Resultado do Tratamento
15.
Anticancer Res ; 39(7): 3909-3916, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262920

RESUMO

BACKGROUND/AIM: This study aimed to identify the survival benefit of intrahepatic tumour control by hepatic arterial infusion chemotherapy (HAIC) in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) or extrahepatic metastasis. PATIENTS AND METHODS: Between 2010 and 2017, a total of 187 consecutive patients with advanced HCC were treated with HAIC. The survival outcomes and response rates to HAIC were analysed. RESULTS: The intrahepatic objective response (OR) rate of all enrolled patients was 18.7%. The survival outcome of patients with OR was significantly better from those without OR, irrespective of initial distant metastasis. Achievement of intrahepatic OR by HAIC and favourable liver function at the time of best response evaluation were two independent factors associated with better OS. CONCLUSION: HAIC-induced intrahepatic tumour reduction significantly prolonged patient survival, irrespective of PVTT or initial distant metastasis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/administração & dosagem , Fluoruracila/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Feminino , Humanos , Infusões Intra-Arteriais , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
BMC Cancer ; 19(1): 693, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307410

RESUMO

BACKGROUND: To evaluate the safety and efficacy of intra-arterial chemotherapy (IAC) for the primary or secondary treatment of infants diagnosed with advanced retinoblastoma before 3 months of age. METHODS: This single-center retrospective study included 39 infants (42 eyes) aged ≤3 months who were diagnosed with unilateral or bilateral advanced intraocular retinoblastoma (group D and E eyes) and received IAC as primary or secondary treatment between June 2012 and February 2017. Based on each patient's therapeutic history and response to chemotherapeutic drugs, melphalan, topotecan, and/or carboplatin were used for IAC. The main outcomes included the technical success rate for IAC, survival rates, and adverse events. RESULTS: In total, 29 and 13 eyes received IAC as primary and secondary treatments, respectively. Catheterization was successful in 136 of 137 procedures. All eyes in the secondary IAC group had previously received intravenous chemotherapy. The mean number of IAC sessions for each eye was 3 (range, 2-6). The 2-year ocular survival rates were 80.7% (95% confidence interval [CI], 58.9-91.7) in the primary IAC group and 91.7% (95% CI, 53.9-98.8) in the secondary IAC group. During the follow-up period, 1 patient with unilateral disease (group E) developed extraocular disease and died. The 2-year recurrence-free survival rates in the primary and secondary IAC groups were 71.9% (95% CI, 49.4-85.7) and 75.0% (95% CI, 40.8-91.2), respectively. During each catheterization procedure, the main complications included eyelid erythema (2.4%), fundus hemorrhage (11.9%), myelosuppression (7.7%), transient vomiting and hair loss (2.6%), and transient pancytopenia (2.6%). Prolonged complications included phthisis bulbi (19.0%), vision loss (19.0%), poor vision (9.5%), and cataract (2.4%). There was no case of stroke, neurological impairment, secondary malignant tumor, or metastasis. CONCLUSIONS: Our findings suggest that IAC, whether primary or secondary, is effective and fairly safe for the management of advanced retinoblastoma in infants aged < 3 months. However, adverse events related to intra-arterial injection and the visual outcomes cannot be neglected and require further investigation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Infusões Intra-Arteriais/efeitos adversos , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico , Vincristina/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/efeitos adversos , Cateterismo/efeitos adversos , Pré-Escolar , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias da Retina/mortalidade , Retinoblastoma/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/efeitos adversos
17.
World Neurosurg ; 131: 234-241, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31351210

RESUMO

BACKGROUND: High-dose bevacizumab delivered via super selective intra-arterial cerebral infusion (SIACI) is one promising clinical trial combination for patients with glioblastoma (GBM). Although both continuous intravenous and intra-arterial administration of bevacizumab, and rechallenge with intravenous bevacizumab, have demonstrated improved survival, this is the first description of rechallenging GBM with SIACI of bevacizumab. CASE DESCRIPTION: We report a case of a 43-year-old woman with recurrent GBM who had received treatment from 3 clinical trials, including a rechallenge with SIACI of bevacizumab. First, she enrolled into a phase I/II trial for patients newly diagnosed with GBM (NCT01811498) and received 3 doses of SIACI bevacizumab over 180 days in addition to standard of care chemotherapy and radiation. Following progression, as indicated on her magnetic resonance imaging scan, she consented for a separate clinical trial for her disease and received 2 cycles of temozolomide with an investigational agent. The patient was removed from the study on tumor progression. Subsequently, she was rechallenged with SIACI of bevacizumab via a third clinical trial (NCT01269853) and then completed 3 intravenous infusions. After completing the third trial, her magnetic resonance imaging scan demonstrated improvement based on Response Assessment In Neuro-Oncology criteria. CONCLUSIONS: This is the first report to highlight the effect of rechallenging a patient with SIACI of bevacizumab following disease progression after initial bevacizumab treatment and subsequent alternate clinical trial failure. There is a need to conduct further clinical trials to evaluate the benefits of rechallenge with SIACI versus intravenous bevacizumab for GBM and further explore theories of bevacizumab resistance.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Ensaios Clínicos como Assunto , Terapia Combinada , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Drogas em Investigação/administração & dosagem , Evolução Fatal , Feminino , Glioblastoma/radioterapia , Glioblastoma/cirurgia , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Imagem por Ressonância Magnética , Retratamento/métodos , Resultado do Tratamento
18.
Neuroradiology ; 61(9): 1083-1091, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31332478

RESUMO

PURPOSE: Purposes are (1) to measure main radiation parameters and (2) to propose a method to estimate the absorbed doses of internal organs starting from DAP values. Measuring the exposition of internal organs by repeated irradiations on an anthropomorphic phantom with the same settings used in vivo, we could establish correlations between (1) DAP and the dose recorded by a dosimeter placed along the X-ray beam entrance pathway; (2) the dose recorded by the same dosimeter and the absorbed dose in internal organs. METHODS: Forty-four consecutive patients (16 males, 28 females) (mean age 35.4 months) treated at our institution with IAC (216 procedures: 196 via the ICA and 20 into branches of the ECA) were included in this prospective study. IAC was divided into 5 phases. Fluoroscopic time, DAP, and ESD were measured. RESULTS: The mean DAP was 595 ± 445 cGy cm2 and the mean fluoroscopic time was 540 ± 403 s. ESD was on average 9.59 mGy (range 0.8-165 mGy). The absorbed dose was lower than 12.1 mGy in the left retina (the more exposed organ) in 75% of single treatments and lower than 25 mGy in 95% of treatments. In the cases of 3 and 6 sessions, the left retina of 75% of patients absorbed respectively less than 36.3 and 72.7 mGy, whereas the left retina of 95% of patients received less than 75.2 and 150.4 mGy. Other organs were less exposed. CONCLUSION: This paper describes a method of absorbed dose estimation providing ranges used clinically in a single practice and the basis for further prospective studies.


Assuntos
Antineoplásicos/administração & dosagem , Fluoroscopia , Doses de Radiação , Neoplasias da Retina/diagnóstico por imagem , Retinoblastoma/diagnóstico por imagem , Adolescente , Angiografia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Infusões Intra-Arteriais , Masculino , Imagens de Fantasmas , Estudos Prospectivos , Radiometria , Neoplasias da Retina/tratamento farmacológico , Retinoblastoma/tratamento farmacológico
19.
Neurology ; 93(5): e458-e466, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31278116

RESUMO

OBJECTIVE: Delayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts. MATERIALS: Data from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed. RESULTS: The final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], p < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, p < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, p = 0.0001) and unfavorable outcome (44% vs 50.6%, p = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome. CONCLUSIONS: A preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.


Assuntos
Angioplastia com Balão/métodos , Isquemia Encefálica/prevenção & controle , Procedimentos Endovasculares/métodos , Nimodipina/administração & dosagem , Hemorragia Subaracnóidea/terapia , Vasodilatadores/administração & dosagem , Vasoespasmo Intracraniano/terapia , Adulto , Idoso , Pressão Arterial , Isquemia Encefálica/etiologia , Feminino , Mortalidade Hospitalar , Humanos , Infusões Intra-Arteriais , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/complicações , Fatores de Tempo , Vasoespasmo Intracraniano/complicações
20.
Int J Neurosci ; 129(10): 1039-1044, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31203689

RESUMO

Aim: Calcineurin (CaN) is a threonine/phosphatase which play roles in neuronal homeostasis. Ischemic stroke induces hyperactivation of CaN which further triggers apoptotic signaling. CaN inhibition has limited therapeutic output and neurotoxicity due to its intricate roles in the neuronal network and requires a strategic modulation. Intra-arterial (IA) mesenchymal stem cells (MSCs) have shown to interact with the milieu in a paracrine manner as compared to CaN inhibitors to ameliorate the neuronal damage triggered by ischemia/reperfusion injury. The present study investigates the role of IA MSCs in modulating neuronal CaN after stroke onset. Materials and methods: To validate, middle-aged ovariectomized female rats exposed to MCAo (90 min) were treated with IA MSCs (1 × 105 MSCs) or phosphate-buffered saline (PBS) at 6 hours to check CaN expression in different groups.Tests for assessing functional and motor coordination were performed along with biochemical estimations. Furthermore, an inhibition study by non-selective inhibitor of neuronal calcium channel, flunarizine, was performed to explore the possible underlying mechanism by which IA MSCs may interact with CaN. Results: The study suggests that IA MSCs seemingly reduce the expression of CaN after ischemic stroke. IA MSCs have shown to improve the functional outcome and normalize oxidative parameters. Conclusion: Our study provides a preliminary evidence of role of IA MSCs in modulating CaN expression.


Assuntos
Isquemia Encefálica/metabolismo , Calcineurina/biossíntese , Transplante de Células-Tronco Mesenquimais/métodos , Neurônios/metabolismo , Neuroproteção/fisiologia , Acidente Vascular Cerebral/metabolismo , Animais , Isquemia Encefálica/terapia , Feminino , Infusões Intra-Arteriais , Ovariectomia/efeitos adversos , Ovariectomia/tendências , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/terapia
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