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2.
Arq Bras Cir Dig ; 33(1): e1484, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32236290

RESUMO

BACKGROUND: Hepatectomies promote considerable amount of blood loss and the need to administrate blood products, which are directly linked to higher morbimortality rates. The blood-conserving hepatectomy (BCH) is a modification of the selective vascular occlusion technique. It could be a surgical maneuver in order to avoid or to reduce the blood products utilization in the perioperative period. AIM: To evaluate in rats the BCH effects on the hematocrit (HT) variation, hemoglobin serum concentration (HB), and on liver regeneration. METHODS: Twelve Wistar rats were divided into two groups: control (n=6) and intervention (n=6). The ones in the control group had their livers partially removed according to the Higgins and Anderson technique, while the rats in the treatment group were submitted to BCH technique. HT and HB levels were measured at day D0, D1 and D7. The rate between the liver and rat weights was calculated in D0 and D7. Liver regeneration was quantitatively and qualitatively evaluated. RESULTS: The HT and HB levels were lower in the control group as of D1 onwards, reaching an 18% gap at D7 (p=0.01 and p=0.008, respectively); BCH resulted in the preservation of HT and HB levels to the intervention group rats. BCH did not alter liver regeneration in rats. CONCLUSION: The BCH led to beneficial effects over the postoperative HT and serum HB levels with no setbacks to liver regeneration. These data are the necessary proof of evidence for translational research into the surgical practice. A) Unresected liver; B) liver appearance after the partial hepatectomy (1=vena cava; 2=portal vein; 3=hepatic vein; 4=biliary drainage; 5=hepatic artery).


Assuntos
Hepatectomia/métodos , Regeneração Hepática , Fígado/irrigação sanguínea , Fígado/cirurgia , Veias/fisiologia , Animais , Volume Sanguíneo/fisiologia , Hematócrito , Hemoglobinas/análise , Hepatopatia Veno-Oclusiva/fisiopatologia , Masculino , Veia Porta/cirurgia , Período Pós-Operatório , Ratos , Ratos Wistar
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 242-247, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027284

RESUMO

OBJECTIVE: To investigate the preventive and therapeutic effects of endothelial progenitor cells on monocrotaline-induced hepatic vein occlusion disease in mice. METHODS: C57BL/6 mice were randomly divided into 3 groups: saline group (n=15), monocrotaline group (n=15), and endothelial progenitor cell infusion group (n=15). Liver function (TBIL, ALT, AST), liver index, and serum levels of TNF-α and IL-6 were measured on the 8th day after intragastric administration. Hepatic sinusoidal endothelial cells, hepatic central venous endothelial cells and hepatocytes were observed by both HE and immunohistochemical staining. Hepatic fibrosis was observed by Masson's trichrome staining. RESULTS: By the light microscopy, the liver of the monocrotaline group showed moderate to the severe injuries of hepatic sinusoidal and central venous endothelial cells, and hepatic venous congestion. Masson staining showed moderate to severe hepatic fibrosis of central vein and hepatic sinus. In the endothelial progenitor cell group, hepatic sinusoidal and central venous endothelial cell injuries, and the fibrosis of central hepatic vein and hepatic sinus were mild to moderate. Hepatic venous congestion was reduced in comparison with that in the mice of the monocrotaline group. Compared with the endothelial progenitor cell group, the liver index was higher, the liver function was more abnormal, and the serum expression levels of TNF-α and IL-6 were higher in the monocrotaline group. CONCLUSION: The monocrotaline-induced damage of hepatic sinusoidal and central venous endothelial cells is an linitiating factor for hepatic vein occlusive disease. Infusion of endothelial progenitor cells can play a role in preventing and treating hepatic vein occlusion.


Assuntos
Células Progenitoras Endoteliais , Hepatopatia Veno-Oclusiva , Animais , Veias Hepáticas , Fígado , Camundongos , Camundongos Endogâmicos C57BL , Monocrotalina
4.
Toxicol Lett ; 323: 41-47, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982501

RESUMO

Gynura japonica (also named Tusanqi in Chinese) is used as a folk herbal medicine for treating blood stasis or traumatic injury. However, hundreds of hepatic sinusoidal obstruction syndrome (HSOS) cases have been reported after consumption of preparations made from G. japonica because it contains large amounts of hepatotoxic pyrrolizidine alkaloids (PAs). To date, blood pyrrole-protein adducts (PPAs) are suggested as biomarkers for the diagnosis of PA-induced HSOS in clinics. However, the concentration of PPAs in the blood is greatly affected by several factors including the amount of PA exposure, herb intake period, and blood sampling time after the last exposure. In present study, the kinetic characters of PPAs in serum and liver as well as other potential target organs were studied systematically and comprehensively following multiple exposures of PAs in G. japonica extract (GJE). As results, PPAs content reached to a plateau both in serum and liver after the mice were treated with GJE for 2 weeks on daily basis. PPAs cleared significantly slower in liver (T1/2ke∼184.6 h, ∼7.7 days) than in serum (T1/2ke∼95.8 h, ∼4.0 days). Although more than 90 % PPAs were removed 2 weeks after the last dosing, PPAs still persisted in the liver until the end of the experiment, i.e. 8 weeks after the last dosing. The results would be of great help for understanding the importance of PPAs for PA-induced toxicity and its detoxification.


Assuntos
Proteínas Sanguíneas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Hepatopatia Veno-Oclusiva/induzido quimicamente , Pirróis/metabolismo , Alcaloides de Pirrolizidina/farmacocinética , Animais , Medicamentos de Ervas Chinesas/toxicidade , Cinética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Extratos Vegetais/toxicidade , Alcaloides de Pirrolizidina/toxicidade
5.
Lancet Haematol ; 7(1): e61-e72, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31818728

RESUMO

Sinusoidal obstructive syndrome, also known as hepatic veno-occlusive disease, is a potentially life-threatening complication that occurs in children undergoing haemopoietic stem-cell transplantation (HSCT). Differences in the incidence of genetic predisposition and clinical presentation of sinusoidal obstructive syndrome between children and adults have rendered the historical Baltimore and Seattle diagnostic criteria insufficient for children. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) proposed the first paediatric diagnostic and severity grading guidelines for sinusoidal obstructive syndrome, intended for implementation across European centres. However, universally accepted paediatric criteria are needed to ensure prompt diagnosis, definitive treatment, and improved outcomes for children, adolescents, and young adults with sinusoidal obstructive syndrome, and to facilitate international clinical research collaboration. We convened an international panel of multidisciplinary experts including physicians with expertise in HSCT, paediatric intensive care, nephrology, hepatology, radiology, pathology, and transfusion medicine; HSCT advanced-practice providers and medical trainees; pharmacists; and translational and basic science researchers from the Pediatric Acute Lung Injury and Sepsis Investigators Network, the EBMT, the Pediatric Blood and Marrow Transplant Consortia, and several other institutions with extensive experience in sinusoidal obstructive syndrome. Panellists convened at The University of Texas, MD Anderson Cancer Center (Houston, TX, USA) in February, 2019, to evaluate the available evidence. In this expert position statement paper, we provide consensus recommendations for the international implementation of guidelines for the diagnosis, severity grading, and treatment of sinusoidal obstructive syndrome among children, adolescents, and young adults. We endorse universal adoption of paediatric diagnostic guidelines for sinusoidal obstruction syndrome as proposed by the EBMT, and provide implementation guidance for standardisation across centres; we have further proposed adjunctive use of age-appropriate organ-specific toxicity criteria for severity grading and provided prophylaxis and treatment considerations among children and adolescent and young adult patients. Key recommendations include: (1) liver biopsy, portal venous wedge pressure, and reversal of portal venous flow on Doppler ultrasonography should not be used for the routine diagnosis of sinusoidal obstructive syndrome in children, adolescents, and young adults; (2) platelet refractoriness can be defined as a corrected count increment of less than 5000-7500 following at least two sequential ABO-compatible fresh platelet transfusions; (3) hepatomegaly is best defined as an absolute increase of at least 1 cm in liver length at the midclavicular line; and if a baseline measurement is not available, hepatomegaly can be defined as greater than 2 SDs above normal for age; and (4) the presence and volume of ascites can be categorised as mild (minimal fluid by liver, spleen, or pelvis), moderate (<1 cm fluid), or severe (fluid in all three regions with >1 cm fluid in at least two regions).


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva , Adolescente , Bilirrubina/análise , Biomarcadores/análise , Criança , Colagogos e Coleréticos/uso terapêutico , Feminino , Fibrinolíticos/uso terapêutico , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/terapia , Humanos , Masculino , Polidesoxirribonucleotídeos/uso terapêutico , Fatores de Risco , Índice de Gravidade de Doença , Ultrassonografia Doppler , Ácido Ursodesoxicólico , Adulto Jovem
6.
Transplant Proc ; 51(9): 3159-3162, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31711585

RESUMO

BACKGROUND: Allogenic hematopoietic stem cell transplantation may be the best currently available method to treat relapsed hemophagocytic lymphohistiocytosis (HLH) related to Epstein-Barr virus. The high rate of transplantation-related complications was initially the main obstacle preventing the wider adoption of this protocol; however, the previously more common complications, such as infection and graft failure, have fallen to very low levels with the development of new drugs and methods. Some other complications, such as veno-occlusive disease and transplantation associated thrombotic microangiopathy, are rare after allogenic hematopoietic stem cell transplantation, but the morbidity and mortality associated with them are very high. CASE PRESENTATION: A patient with relapsed HLH related to Epstein-Barr virus showed the sequential severe complications of veno-occlusive disease, transplantation-associated thrombotic microangiopathy, and acute graft-vs-host disease after haploidentical transplantation. This patient was successfully treated by stopping administration of calcineurin inhibitors and instead treating with defibrotide, rituximab, CD25 monoclonal antibody, atorvastatin calcium tablets, methylprednisolone, budesonide, continuous plasma exchange, and bedside ultrafiltration. At the last follow-up, the patient had been living disease free for 2 years without any other complications. CONCLUSION: Epstein-Barr virus related-HLH patients have severe clinical features and currently poor prognosis. Allogenic hematopoietic stem cell transplantation may be the best way to treat this disease; however, the management of related complications is vital in the improvement of long-term survival.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Linfo-Histiocitose Hemofagocítica/cirurgia , Microangiopatias Trombóticas/etiologia , Criança , Infecções por Vírus Epstein-Barr/complicações , Feminino , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Hepatopatia Veno-Oclusiva/terapia , Herpesvirus Humano 4 , Humanos , Linfo-Histiocitose Hemofagocítica/virologia , Recidiva , Microangiopatias Trombóticas/terapia
7.
PLoS One ; 14(11): e0224659, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31689340

RESUMO

BACKGROUND: Hepatic venous-occlusive disease is blockage of microscopic veins in the liver causing 20-50% mortality. Ingestion of pyrrolizidine alkaloid plant, radiation therapy, and post-bone-marrow-transplant reactions are the commonest causes. In Ethiopia, a venous-occlusive disease outbreak was identified in 2002 in Tahtay Koraro district, Tigray. Suspected due to ingestion of the toxic pyrrolizidine alkaloid plant Ageratum conyzoids, found throughout the district. We aimed to describe the surveillance data of venous-occlusive disease from September 2006 to August 2016 in Tahtay koraro district, Ethiopia, 2017. METHODOLOGY: We defined a possible Hepatic venous-occlusive disease case as any patient with abdominal pain for at least 2 weeks, abdominal distention, and hepato-splenomegaly during September 2006-August 2016. We reviewed previous district line lists, weekly reports, and clinical records to identify and describe cases. Agricultural interventions were obtained from the agricultural offices of the district. RESULT: We identified 179 possible cases with 83 deaths with a case-fatality rate of 46.3%. Among cases, 110 (61.5%) were males and 113 (63%) were >15 years. In total, 164 (91.6%) cases were from one village (Kelakil). The pick number of cases of VOD in this village was during 2008/09 which was 1076. The highest incidence (86/100,000) occurred in 2008. During the study period, 2,746 years of potential life were lost due to Hepatic venous-occlusive disease. Mechanical removal of the Ageratum started in 2011. CONCLUSION: Hepatic venous-occlusive disease was an ongoing problem in Tahtay Koraro; However, the problem has largely been alleviated by displacing people from the affected area and removing the causative weed. More research is needed to understand why Kelakil village was more affected despite the widespread presence of the weed. Chemical and mechanical removal of the Ageratum could strengthen intervention activities.


Assuntos
Ageratum/toxicidade , Surtos de Doenças/estatística & dados numéricos , Hepatopatia Veno-Oclusiva/epidemiologia , Alcaloides de Pirrolizidina/toxicidade , Controle de Plantas Daninhas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos Transversais , Surtos de Doenças/prevenção & controle , Etiópia/epidemiologia , Feminino , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/prevenção & controle , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Rev. esp. enferm. dig ; 111(11): 823-827, nov. 2019. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-190504

RESUMO

Background and aims: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). Methods: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-alfa), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. Results: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-alfa, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. Conclusions: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS


No disponible


Assuntos
Animais , Ratos , Salvia miltiorrhiza , Extratos Vegetais/farmacocinética , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Moléculas de Adesão Celular/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos , Fator de Transcrição RelA/efeitos dos fármacos , Modelos Animais de Doenças , Hepatopatia Veno-Oclusiva/induzido quimicamente , Testes de Função Hepática/métodos , Substâncias Protetoras/análise
9.
Int J Hematol ; 110(6): 709-722, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31655984

RESUMO

Inotuzumab ozogamicin (InO) is a targeted treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). InO was previously studied in INO-VATE, an international, open-label, randomized phase 3 trial comparing InO against standard of care (SoC). In the present subgroup analysis, we evaluated outcomes in the 55 Asian patients who were randomized in INO-VATE (31 InO and 24 SoC). Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was achieved in 22/31 patients treated with InO versus 5/24 treated with SoC. In the InO arm, more of the patients achieving CR/CRi were minimal residual disease (MRD)-negative (17/22 versus 1/5), and more patients proceeded directly to hematopoietic stem cell transplantation (15/31 versus 3/24). Median overall survival for the respective arms was 5.8 versus 3.9 months (hazard ratio 0.67; 97.5% CI 0.28, 1.62). In the safety analysis (n = 51), the most common adverse events were hematologic. Sinusoidal obstruction syndrome was reported in five InO patients and one SoC patient. In conclusion, Asian patients with relapsed or refractory B-cell ALL experienced improved efficacy with InO versus SoC, with an efficacy and safety profile consistent with results of the overall INO-VATE population.Clinical trial registration: ClinicalTrials.gov identifier: NCT01564784.


Assuntos
Inotuzumab Ozogamicina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Terapia de Salvação/métodos , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Inotuzumab Ozogamicina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Indução de Remissão/métodos , Terapia de Salvação/efeitos adversos , Terapia de Salvação/normas , Padrão de Cuidado
10.
Semin Thromb Hemost ; 45(8): 767-777, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31627217

RESUMO

Defibrotide has been approved in several geographic jurisdictions for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) for years. However, available data on efficacy and safety for its use in VOD are contrasting. We performed a meta-analysis to evaluate the efficacy and safety of defibrotide in the treatment of hepatic VOD/SOS post-hematopoietic stem cell transplantation (HSCT). PubMed and Embase were searched for studies regarding the efficacy and safety of defibrotide in VOD patients. Survival rate at day + 100 post-HSCT (D + 100 SR), as well as the prognosis, comprising complete response (CR), adverse events including ≥1 adverse event (≥1 AE), hemorrhage, and serious adverse events (SAEs), were pooled using a random effect model. Sixteen studies involving 3,002 participants were included. Pooled estimates for overall D + 100 SR as well as rate of CR, ≥1 AE, hemorrhage, SAEs in VOD patients post-HSCT were 58% (95% CI: 54-62%), 57% (95% CI: 45-68%), 65% (95% CI: 54-75%), 16% (95% CI: 5-27%), 53% (95% CI: 51-55%), respectively, and were 44% (95% CI: 39-48%), 39% (95% CI: 28-50%), 88% (95% CI: 71-100%), 42% (95% CI: 30-55%), 58% (95% CI: 52-64%), respectively, in severe VOD (sVOD) patients. Hemorrhage and hypotension were the most common AEs. Current evidence suggests that defibrotide improves the D + 100 SR and CR in VOD/sVOD patients following HSCT. However, the results of this review/meta-analysis were mainly based on data from observational studies, potentially subject to selection bias. Consequently, higher quality randomized control trials and larger prospective cohort studies are warranted.


Assuntos
Fibrinolíticos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Polidesoxirribonucleotídeos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Fibrinolíticos/farmacologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Polidesoxirribonucleotídeos/farmacocinética , Adulto Jovem
11.
World J Gastroenterol ; 25(28): 3753-3763, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31391770

RESUMO

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.


Assuntos
Veias Hepáticas/patologia , Hepatopatia Veno-Oclusiva/diagnóstico , Plantas Comestíveis/toxicidade , Alcaloides de Pirrolizidina/toxicidade , Anticoagulantes/uso terapêutico , Biópsia , China , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Hidratação/métodos , Glucocorticoides , Veias Hepáticas/citologia , Veias Hepáticas/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/terapia , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Testes de Função Hepática , Transplante de Fígado , Imagem por Ressonância Magnética , Plantas Comestíveis/química , Derivação Portossistêmica Transjugular Intra-Hepática , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
Pediatr Blood Cancer ; 66(11): e27964, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31407508

RESUMO

Secondary hemophagocytic syndrome (HPS) has been described after autologous hematopoietic cell transplant (AutoHCT). We report two cases of secondary HPS after novel consolidation therapy for high-risk neuroblastoma as part of an institutional phase 2 trial incorporating immunotherapy into a "standard" AutoHCT regimen. Both patients developed liver dysfunction beyond expected course of hepatic veno-occlusive disease, coagulopathy, hyperferritinemia, and when evaluated, elevated soluble interleukin-2 receptor and hemophagocytosis. These cases highlight the need for clinicians to have a high index of suspicion for immune-related complications in patients receiving immune therapies.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia/efeitos adversos , Células Matadoras Naturais/transplante , Falência Hepática/etiologia , Linfo-Histiocitose Hemofagocítica/etiologia , Neuroblastoma/terapia , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Pré-Escolar , Ferritinas/sangue , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Lactente , Falência Hepática/terapia , Linfo-Histiocitose Hemofagocítica/imunologia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Neuroblastoma/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/terapia , Condicionamento Pré-Transplante/efeitos adversos
13.
Anticancer Res ; 39(8): 4549-4554, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366558

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. PATIENTS AND METHODS: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. RESULTS: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. CONCLUSION: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Hepatopatia Veno-Oclusiva/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Complicações Pós-Operatórias/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Hepatectomia , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/patologia , Humanos , Leucovorina/administração & dosagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Complicações Pós-Operatórias/induzido quimicamente , Complicações Pós-Operatórias/patologia , Período Pré-Operatório
14.
Molecules ; 24(12)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31212965

RESUMO

The goal of this study was to investigate the potential for a cannabidiol-rich cannabis extract (CRCE) to interact with the most common over-the-counter drug and the major known cause of drug-induced liver injury-acetaminophen (APAP)-in aged female CD-1 mice. Gavaging mice with 116 mg/kg of cannabidiol (CBD) [mouse equivalent dose (MED) of 10 mg/kg of CBD] in CRCE delivered with sesame oil for three consecutive days followed by intraperitoneally (i.p.) acetaminophen (APAP) administration (400 mg/kg) on day 4 resulted in overt toxicity with 37.5% mortality. No mortality was observed in mice treated with 290 mg/kg of CBD+APAP (MED of 25 mg/kg of CBD) or APAP alone. Following CRCE/APAP co-administration, microscopic examination revealed a sinusoidal obstruction syndrome-like liver injury-the severity of which correlated with the degree of alterations in physiological and clinical biochemistry end points. Mechanistically, glutathione depletion and oxidative stress were observed between the APAP-only and co-administration groups, but co-administration resulted in much greater activation of c-Jun N-terminal kinase (JNK). Strikingly, these effects were not observed in mice gavaged with 290 mg/kg CBD in CRCE followed by APAP administration. These findings highlight the potential for CBD/drug interactions, and reveal an interesting paradoxical effect of CBD/APAP-induced hepatotoxicity.


Assuntos
Acetaminofen/efeitos adversos , Canabidiol/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Animais , Biomarcadores , Canabidiol/química , Cannabis/química , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Camundongos Endogâmicos , Compostos Fitoquímicos/efeitos adversos , Compostos Fitoquímicos/química , Extratos Vegetais/efeitos adversos
15.
Ann Hematol ; 98(7): 1733-1742, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31053879

RESUMO

Hepatic sinusoidal obstruction syndrome (SOS) has been rarely studied after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a retrospective multicentre study on patients with SOS after allo-HSCT in China. The incidence, risk factors, and outcomes were compared between HID HSCT and matched related donor (MRD) HSCT. SOS developed in 0.4% of patients (HIDs: 0.4%, MRDs: 0.5%, p = 0.952) at a median time of 21.50 days (range, 1-55) after allo-HSCT (HIDs: 24 days, MRDs: 20 days, p = 0.316). For patients diagnosed with SOS, the 2-year cumulative incidence of relapse was 22.7% and 22.4% in patients receiving HID and MRD transplantation, respectively (p = 0.584). Overall survival (OS) at 2 year was 10.4% and 38.5% in the two groups (p = 0.113). The transplant-related mortality (TRM) at 100 days was 60.9% in the HID group and 38.5% in the MRD group (p = 0.178). According to the multivariate analyses, significant independent risk factors for the occurrence of SOS were delayed platelet engraftment (p = 0.007) and advanced disease status at the time of HSCT (p = 0.009). The outcomes of SOS after HID HSCT are similar to those after MRD HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Doadores de Tecidos , Condicionamento Pré-Transplante , Adolescente , Adulto , Aloenxertos , Criança , China/epidemiologia , Feminino , Seguimentos , Hepatopatia Veno-Oclusiva/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
16.
Radiographics ; 39(3): 842-856, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31059404

RESUMO

The liver is a unique organ as it receives afferent blood supply from the umbilical vein, portal vein, and hepatic artery in the developing embryo but has only one efferent drainage method, through the hepatic veins. In the postnatal period, about 70% of the afferent blood flow into the liver is from the portal venous system, unique vessels that begin and end in a capillary system. Vascular anomalies of the hepatic artery, hepatic veins, portal vein, and/or umbilical vein can be congenital or acquired secondary to inflammation and/or infection, trauma, systemic disorders, or iatrogenic causes. The vascular anomalies can be incidental findings at imaging, or the infant or child can present with symptoms such as abdominal pain and ascites, be diagnosed with gastrointestinal bleeding, and have abnormal liver function test results. Imaging can demonstrate vascular findings such as shunts, thrombosis, or collaterals; secondary parenchymal findings such as diffuse or focal abnormal enhancement patterns; and parenchymal lesions such as regenerative nodules. This article discusses and illustrates vascular disorders of the liver that may be encountered in the pediatric population. These include (a) normal vascular variants; (b) congenital anomalies (preduodenal portal vein and infradiaphragmatic total anomalous pulmonary venous return); (c) acquired thromboses (extrahepatic portal venous thrombosis); (d) inflammatory vascular conditions, which can result in hepatic artery aneurysms or pseudoaneurysms; (e) hepatic venous outflow disorders (veno-occlusive disease); and shunt lesions. Liver transplantation and associated vascular complications are a large topic and will not be reviewed in this article. Knowledge of the vascular and parenchymal changes seen with these entities can aid imaging diagnosis and guide appropriate management. ©RSNA, 2019.


Assuntos
Artéria Hepática/anormalidades , Veias Hepáticas/anormalidades , Fígado/irrigação sanguínea , Veia Porta/anormalidades , Malformações Arteriovenosas/diagnóstico por imagem , Variação Biológica Individual , Criança , Pré-Escolar , Feminino , Artéria Hepática/diagnóstico por imagem , Veias Hepáticas/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Fígado/diagnóstico por imagem , Fígado/embriologia , Fígado/crescimento & desenvolvimento , Imagem por Ressonância Magnética , Masculino , Veia Porta/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Veias Umbilicais/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem
17.
Pediatr Transplant ; 23(5): e13456, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31081161

RESUMO

Liver stiffness measurement by transient elastography is a non-invasive ultrasound-based technique used mainly for the evaluation of liver fibrosis in patients with chronic liver diseases. Some authors have suggested that it could be useful in the assessment of hepatic complications during hematopoietic stem cell transplant (HSCT), especially veno-occlusive disease (VOD) or sinusoidal obstructive syndrome (SOS). Here, we present the evaluation of liver stiffness in three patients who developed severe hepatic VOD/SOS after HSCT. Liver stiffness measurement values were normal before transplant and afterward until the diagnosis of VOD/SOS when a dramatic increase was observed. After the VOD/SOS specific treatment, the values of stiffness showed a similar pattern of progressive reduction in all the three patients, with normalization after two weeks. In this report, we discuss the role of LSM in the management of patients after the diagnosis of VOD/SOS.


Assuntos
Técnicas de Imagem por Elasticidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Fígado/diagnóstico por imagem , Adolescente , Criança , Feminino , Hepatopatia Veno-Oclusiva/etiologia , Humanos
18.
J Pediatr Hematol Oncol ; 41(6): e395-e401, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30933024

RESUMO

Severe veno-occlusive disease (VOD) following hematopoietic stem cell transplantation has a high mortality rate. The clinical course of VOD, role of preemptive and aggressive supportive care, and outcomes were investigated in a retrospective study from 2007 to 2014. Defibrotide was not available in all but one case with VOD at our center during the study. Forty-nine allogeneic transplants with intravenous busulfan-based or total body irradiation-based myeloablative conditioning were included. The median after hematopoietic stem cell transplantation day for suspicion of developing VOD (pre-VOD phase) was 6 due to weight gain, hepatomegaly, and/or mild increase in total bilirubin without fulfilling the modified Seattle criteria in 22 cases (45%). Despite fluid restriction, aggressive diuresis, and fresh frozen plasma infusions, 16 patients (33%) developed VOD by +10 days. Five cases (31%) had severe, 9 (56%) moderate, and 2 (13%) mild VOD. Eight cases (50%) required transfer to intensive care. One patient was given defibrotide, which was later discontinued due to concerns of adverse effects. Day +100 survival was 100% with complete resolution of VOD. Preemptive and aggressive supportive care could help achieve favorable outcomes in VOD and may have ameliorated the severity. This approach may be combined with other measures in the prevention/treatment of VOD.


Assuntos
Doenças Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Hepatopatia Veno-Oclusiva/diagnóstico , Agonistas Mieloablativos/uso terapêutico , Cuidados Paliativos/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doenças Hematológicas/patologia , Doenças Hematológicas/terapia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
19.
J Pediatr Hematol Oncol ; 41(5): e296-e301, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30933028

RESUMO

Thalassemia is a major public health problem in developing countries. Sibling matched hematopoietic stem cell transplantation (HCT) is the recommended treatment for thalassemia major (TM). We retrospectively analyzed our data of thalassemia major patients who underwent HCT at a tertiary care center in Northern India from January 2008 to September 2017. The primary end points were overall survival (OS) and thalassemia-free survival (TFS), and secondary end points were complications post HCT (graft-versus-host-disease [GVHD], hemorrhagic cystitis [HC], and sinusoidal obstruction syndrome [SOS]). Data of 203 transplants for 200 patients (3 s transplants) were evaluated. Median follow-up period was 29.1 months (range, 0.3 to 116.7 mo). The overall survival (OS) was 88.5% and TFS was 82%. Class risk analysis showed a significantly higher OS and TFS in class I and class II compared to class III high risk group (OS: P=0.0017; TFS: P=0.0005) and (OS: P=0.0134; TFS: P=0.0027) respectively. Acute and chronic GVHD was seen in 59 (29.5%) and 18 (9%) patients, respectively, and SOS and HC were seen in 23 (11.5%) and 11 (5.5%) patients, respectively. This study reconfirms that allogenic HCT is feasible in developing world with the overall survival and TFS comparable to that reported in Western literature and should be considered early in all TM patients with available matched sibling donors.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/terapia , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Talassemia beta/complicações , Talassemia beta/mortalidade
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