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3.
Anticancer Agents Med Chem ; 19(11): 1388-1398, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31038079

RESUMO

BACKGROUND: Parallel to the safety of liver resections, new chemotherapy drugs have emerged for the control of liver metastases. However, there is unclear evidence about the combination of intensive BVZ-therapy and extended resections. The main aim was to analyse the impact of Bevacizumab (BVZ) in terms of liver safety and tolerability in two experimental models: a basal-toxicity situation and after major hepatectomy. METHODS: Eighty male-Wistar rats were grouped as toxicity analysis (sham-operated rats-OS-) and regeneration after- surgery analysis (hepatectomy rats-H-). Eight further subgroups were created according to sacrifice (6- hours-6h- or 24-hours-24h-) and dose (µg) of BVZ (none, 100, 200, 400). Several measurements were performed, including biochemical serum samples, histopathological analysis, cytokines (IL-6, TNF-α, TGF-ß), oxidative-stress (GSH/GSSG, ATP), lipid-peroxidation (TBARS) and epidermal and vascular endothelium growth-factors (EGF and VEGF). RESULTS: In the toxicity analysis, safe results with BVZ were observed, with no significant differences among the groups. A trend towards a lower oxidative status was observed in the OS 6 h-100, -200 and -400 versus the OS 6 h-none group. Similar results were observed in the hepatectomy model, with stable oxidative-stress-index and IL-6, TNF- α, and TGF- ß levels. Despite higher lipid peroxidation status, overall regeneration was preserved. As expected, VEGF was almost undetectable in BVZ-treated groups after resection, but not in the non-resection group. CONCLUSION: It was concluded that liver status was not impaired by BVZ even at the high-dose. Similarly, liver regeneration after extended hepatectomy in BVZ-treated animals was well-preserved. Extended liver resections may be encouraged in BVZ-treated patients due to its excellent tolerability and good liver regeneration status.


Assuntos
Bevacizumab/farmacologia , Hepatectomia , Fígado/efeitos dos fármacos , Fígado/cirurgia , Animais , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Cinética , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Estrutura Molecular , Estresse Oxidativo , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Rev. Univ. Ind. Santander, Salud ; 44(3): 49-55, Diciembre 19, 2012. ilus, tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-677538

RESUMO

El pénfigo es una enfermedad vesículo-ampollosa autoinmune de la piel y mucosas, que puede comprometer grandes extensiones; los tipos vulgar y foliáceo son los más frecuentes, con diferencias inmunopatológicas entre ellas. El pénfigo es tratado con corticoides y Azatioprina pero en los últimos años se incluyeron nuevos medicamentos como inmunoglobulinas, Rituximab (anticuerpo monoclonal quimérico anti-CD20) entre otros, Mostramos un caso de pénfigo hiperpigmentado atípico, y revisamos el tema en especial sobre el tratamiento. Salud UIS 2012; 44 (3): 49-55.


Pemphigus is a blistering autoimmune skin and mucous disease, wich can involve large areas; vulgar and foliaceus types are the most common, with immunological differences between them. The pemphigus is treated with corticoids and azathioprine but in recent years new drugs were included as immunoglobulins, Rituximab (Chimeric monoclonal anti-CD20), among others. We show a case of atypical hyperpigmented pemphigus appearance and the review of issue, especially on treatment. Salud UIS 2012; 44 (3): 49-55.

6.
J Surg Res ; 175(1): e1-9, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22341343

RESUMO

BACKGROUND: Liver resection is a feasible treatment for multiple liver diseases. There is no evidence about the impact of age on liver regeneration. OBJECTIVE: To assess the effect of age on liver regeneration in an experimental in vivo animal model of 70%-partial hepatectomy. METHODS: Forty young (Y) and old (O) Wistar male rats (n = 80) were distributed into four groups [controls (C), sham operated (SO), hepatectomy 6 h (H6), and 48 h (H48)]. Different morphometric and biochemical factors, oxidative and nitrosative stress, lipid peroxidation, cytokines kinetics, and histopathologic tissular parameters were determined. RESULTS: Early postoperative mortality was higher in aged rats (P = 0.049). Morphometric determinations, liver regeneration index, and total volume weight were favorable to young rats. Serum transaminase levels were higher in aged rats. Parameters of necrosis (measured by histopathologic injury [HI: 0-I-II-III]), regeneration (measured by bromodeoxyuridine-BrdU incorporation) and apoptosis (determined by the TDT-mediated dUTP nick end labeling-TUNEL) were well-synchronized in young rats. Parameters of oxidative stress such as reduced (GSH), oxidized (GSSG) glutathione and lipid peroxidation (measured by hepatic malondialdehyde -MDA-) were lower in young animals throughout the studied period. Nitrosative stress measured by nitric oxide (NO) end-products was higher in late stages in resected old rats. Pro-inflammatory cytokines (TNF- α) reached higher and earlier levels in aged rats while pro-regenerative cytokines (IL-6) were significantly higher in early stages for young rats and in late stages for aged rats. The levels of TGF-ß were higher in young rats. CONCLUSION: Liver regeneration is delayed and reduced in aged animals submitted to liver resection.


Assuntos
Hepatectomia/mortalidade , Regeneração Hepática/fisiologia , Fígado/fisiologia , Animais , Fígado/patologia , Masculino , Ratos , Ratos Wistar
7.
Cancer Chemother Pharmacol ; 68(1): 267-74, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21499894

RESUMO

PURPOSE: The admitted benefits of intraperitoneal chemotherapy during postoperative administration for the treatment of peritoneal carcinomatosis from ovarian origin are limited by their associated morbidity and restricted diffusion by the presence of multiple intra-abdominal adherences. The purpose of the study was to evaluate the security, effectiveness, and cytoreduction optimization of intraperitoneal paclitaxel administration previously to radical surgery/peritonectomy/HIPEC (hyperthermic intraoperative intraperitoneal chemotherapy) either in monotherapy or combined with intravenous carboplatin. METHODS: Prospective pilot study of 10 patients with ovarian peritoneal carcinomatosis in stage IIIc-FIGO without previous treatment. After staging of the diseases by laparoscopy, five patients received paclitaxel by weekly intraperitoneal administration (60 mg/m(2), 10 cycles), and other five patients additionally received intravenous carboplatin every 21 days (AUC 6, 4 cycles). Subsequently radical surgery/peritonectomy with HIPEC was performed. RESULTS: The presence of moderate abdominal pain was the most common (70%) side effect associated with neoadjuvant paclitaxel intraperitoneal administration. The intravenous carboplatin administration was not associated with significant increase in adverse effects. It boosted intraperitoneal paclitaxel-associated antitumoral activity with a high average decrease in Index Cancer Peritoneal (21.2 vs. 14.4, P = 0.066) and CA 125(1,053 vs. 346, P = 0.043). All the patients who received combined neoadjuvant chemotherapy obtained R0 cytoreduction. Five-year overall survival was 62%. CONCLUSIONS: The intraperitoneal paclitaxel weekly administration combined with intravenous carboplatin administration prior to radical surgery/peritonectomy with HIPEC is a safe and effective option in the treatment of ovarian peritoneal carcinomatosis. This study shows the possibility to investigate other forms of intraperitoneal chemotherapy and their combinations thoroughly.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma/patologia , Carcinoma/secundário , Carcinoma/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Hipertermia Induzida , Injeções Intraperitoneais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
8.
J Gastrointest Surg ; 15(8): 1459-67, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21512847

RESUMO

BACKGROUND: The involvement of bone marrow hematopoietic stem cells (BMHSC) mobilization during liver regeneration from hepatectomized patients is under debate. The main aim of this study was to investigate the role of BMHSC mobilization after hepatic resection in 33 patients with liver disease. METHODS AND RESULTS: Mobilization of CD34(+) BMHSC after 72 h of surgery was found in peripheral blood of some, but not all, of the hepatectomized patients. These CD34(+) cells co-expressed other stem cells markers. The patients without BMHSC mobilization showed high levels of circulating and liver tissue BMHSC (CD34(+) cells) previous to surgery. Therefore, two types of patients: "mobilizers" and "non-mobilizers" were distinguished based on the values of CD34(+) cells before and after surgery. Changes in cytokines involved in the hepatic regeneration (HGF and TGF-ß), and in BMHSC mobilization process (SCF, SDF-1, IL-12, or MMP-2), were detected in both groups. In addition, a higher activation previous to surgery of the SDF-1/CXCR4 axis in liver tissue was observed in non mobilizers patients compared to mobilizer patients. CONCLUSION: BMHSC mobilization seems to be associated with variations in the levels of cytokines and proteolytic enzymes involved in hepatic regeneration and bone marrow matrix degradation. Hepatectomy may be an insufficient stimulus for BMSHC mobilization. The pre-hepatectomy higher levels CD34(+) cells in peripheral blood and liver, associated to the activation of hepatic SDF-1/CXCR4 axis, suggest a BMHSC mobilization process previous to surgery in non mobilizer patients.


Assuntos
Antígenos CD34/metabolismo , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Regeneração Hepática/fisiologia , Transdução de Sinais/fisiologia , Adolescente , Adulto , Idoso , Quimiocina CXCL12/sangue , Feminino , Células-Tronco Hematopoéticas/fisiologia , Hepatectomia , Fator de Crescimento de Hepatócito/sangue , Humanos , Interleucina-12/sangue , Antígeno Ki-67/metabolismo , Fígado/metabolismo , Fígado/patologia , Fígado/cirurgia , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Receptores CXCR4/sangue , Fator de Células-Tronco/sangue , Fator de Crescimento Transformador beta/sangue
9.
Arch Surg ; 145(5): 482-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20479348

RESUMO

OBJECTIVE: To examine the effectiveness of fibrin sealants as supportive treatment to improve hemostasis and decrease the incidence of bile leakage and intra-abdominal collections. DESIGN: Prospective, controlled, quasiexperimental study. SETTING: Tertiary referral center, University Hospital Reina Sofía. PATIENTS: A total of 115 patients (58 in the control group and 57 in the collagen sponge group) scheduled for conventional hepatectomies. INTERVENTIONS: Patients were distributed into groups for major and minor hepatectomies with or without application of a carrier-bound collagen sponge on the raw surface of the liver. MAIN OUTCOME MEASURES: The main outcome measures were postoperative mortality, incidence and severity of postoperative surgical complications, and length of hospital stay. The secondary outcome measures were postoperative drainage output volume, transfusion requirements, and changes in biochemical parameters (hemoglobin, bilirubin, alanine aminotransferase, and platelet levels). RESULTS: The fibrin sealant after major liver resection was effective for decreasing drainage volume (mean [SD] volume, 1124.7 [842.8] mL in the control group and 691.2 [499.5] mL in the collagen sponge group; P = .007) with a higher volume of output by drain each postoperative day in the control patients (P = .003); postoperative blood transfusion requirements (18.9% vs 7.0%, respectively; P = .04); moderate to severe postoperative complications (21% vs 8%, respectively; P = .03); and mean (SD) hospital stay (12.6 [6.7] vs 9.6 [5.1] days, respectively; P = .03). CONCLUSION: The use of a new carrier-bound collagen sponge after major liver resection may be recommended because of its clinical and cost-savings effectiveness.


Assuntos
Fibrinogênio/uso terapêutico , Hemostasia Cirúrgica/métodos , Hepatectomia/efeitos adversos , Hepatopatias/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Trombina/uso terapêutico , Adulto , Idoso , Transfusão de Sangue , Drenagem , Portadores de Fármacos , Combinação de Medicamentos , Feminino , Humanos , Tempo de Internação , Hepatopatias/complicações , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
10.
Liver Transpl ; 15(1): 37-48, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19109846

RESUMO

The aim of this study was to determine the influence of donor graft steatosis on overall outcome, viral recurrence, and fibrosis progression in orthotopic liver transplantation (OLT) for hepatitis C virus (HCV) cirrhosis. One hundred twenty patients who underwent OLT for HCV cirrhosis between 1995 and 2005 were included in the study. Donor steatosis was categorized as absent (0%-10%; n = 40), mild (10%-30%; n = 32), moderate (30%-60%; n = 29), or severe (>60%; n = 19). A Cox multivariate analysis for marginal donor variables and a Model for End-Stage Liver Disease index were performed. Fibrosis evolution was analyzed in liver biopsies (fibrosis < 2 or > or =2) 3, 6, and 12 months post-OLT and in the late post-OLT period. Fifty-six grafts were lost (46%). The survival of the grafts was inversely proportional to donor liver steatosis: 82%, 72%, and 72% at 1, 2, and 3 years post-OLT in the absence of steatosis; 73%, 63%, and 58% with mild steatosis; 74%, 62%, and 43% with moderate steatosis; and 62%, 49%, and 42% with severe steatosis (P = 0.012). HCV recurrence was earlier and more frequent in recipients with steatosis > 30% (46% versus 32% at 3 months, P = 0.017; 58% versus 43% at 6 months, P = 0.020; 70% versus 56% at 12 months, P = 0.058; and 95% versus 69% at 3 years post-OLT, P = 0.0001). Graft survival was lower in alcoholic liver disease recipients versus HCV recipients when steatosis was >30% at 3, 6, and 12 months post-OLT (P = 0.042) but not when steatosis was <30% (P = 0.53). A higher fibrosis score was obtained 3 months post-OLT (P = 0.033), 6 months post-OLT (P = 0.306), 12 months post-OLT (P = 0.035), and in the late post-OLT period (P = 0.009). In conclusion, donor graft steatosis influences the outcome of OLT for HCV cirrhosis. HCV recurrence is more frequent and earlier in recipients of moderately and severely steatotic livers. Fibrosis evolution is higher when graft steatosis is >30%. OLT with >30% steatotic donor livers should be precluded in HCV recipients.


Assuntos
Hepatite C/terapia , Cirrose Hepática/terapia , Transplante de Fígado/métodos , Adolescente , Adulto , Idoso , Biópsia , Criança , Fígado Gorduroso/virologia , Feminino , Humanos , Fígado/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Resultado do Tratamento
11.
World J Gastroenterol ; 14(38): 5920-3, 2008 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-18855995

RESUMO

We report an unusual pathological entity of a pseudoaneurysm of the right hepatic artery, which developed two years after the resection of a type II hilar cholangiocarcinoma and secondary to an excessive skeletonization for regional lymphadenectomy and neoadjuvant external-beam radiotherapy. After a sudden and massive hematemesis, a multidetector computed tomographic angiography (MDCTA) showed a hepatic artery pseudoaneurysm. Angiography with embolization of the pseudoaneurysm was attempted using microcoils with adequate patency of the hepatic artery and the occlusion of the pseudoaneurysm. A new episode of hematemesis 3 wk later revealed a partial revascularization of the pseudoaneurysm. A definitive interventional radiological treatment consisting of transarterial embolization (TAE) of the right hepatic artery with stainless steel coils and polyvinyl alcohol particles was effective and well-tolerated with normal liver function tests and without signs of liver infarction.


Assuntos
Falso Aneurisma/etiologia , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Colangiocarcinoma/cirurgia , Artéria Hepática , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/terapia , Quimioterapia Adjuvante , Embolização Terapêutica , Hematemese/etiologia , Artéria Hepática/diagnóstico por imagem , Humanos , Excisão de Linfonodo , Masculino , Terapia Neoadjuvante , Radiografia Intervencionista , Radioterapia Adjuvante , Recidiva , Resultado do Tratamento
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