RESUMEN
Hepatoblastoma (HB) is the most common type of pediatric liver malignancy, which predominantly occurs in young children (aged <5 years), and continues to be a therapeutic challenge in terms of metastasis and drug resistance. As a new pattern of tumor blood supply, vasculogenic mimicry (VM) is a channel structure lined by tumor cells rather than endothelial cells, which contribute to angiogenesis. VM occurs in a variety of solid tumor types, including liver cancer, such as hepatocellular carcinoma. The aim of the present study was to elucidate the effect of arsenic trioxide (As2O3) on VM. In vitro experiments identified that HB cell line HepG2 cells form typical VM structures on Matrigel, and the structures were markedly damaged by As2O3 at a low concentration before the cell viability significantly decreased. The western blot results indicated that As2O3 downregulated the expression level of VMassociated proteins prior to the appearance of apoptotic proteins. In vivo, VM has been observed in xenografts of HB mouse models and identified by periodic acidSchiff+/CD105 channels lined by HepG2 cells without necrotic cells. As2O3 (2 mg/kg) markedly depresses tumor growth without causing serious adverse reactions by decreasing the number of VM channels via inhibiting the expression level of VMassociated proteins. Thus, the present data strongly indicate that low dosage As2O3 reduces the formation of VM in HB cell line HepG2 cells, independent of cell apoptosis in vivo and in vitro, and may represent as a candidate drug for HB targeting VM.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Arsenicales/farmacología , Hepatoblastoma/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Óxidos/farmacología , Animales , Apoptosis , Trióxido de Arsénico , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Hepatoblastoma/irrigación sanguínea , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Masculino , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hepatoblastoma is the most common liver tumor of early childhood, which is usually characterized by unusual hypervascularity. Recently, long non-coding RNAs (lncRNA) have emerged as gene regulators and prognostic markers in several cancers, including hepatoblastoma. We previously reveal that lnRNA-TUG1 is upregulated in hepatoblastoma specimens by microarray analysis. In this study, we aim to elucidate the biological and clinical significance of TUG1 upregulation in hepatoblastoma. We show that TUG1 is significantly upregulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. TUG1 knockdown inhibits tumor growth and angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, migration, and invasion in vitro. TUG1, miR-34a-5p, and VEGFA constitutes to a regulatory network, and participates in regulating hepatoblastoma cell function, tumor progression, and tumor angiogenesis. Overall, our findings indicate that TUG1 upregulation contributes to unusual hypervascularity of hepatoblastoma. TUG1 is a promising therapeutic target for aggressive, recurrent, or metastatic hepatoblastoma.
Asunto(s)
Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/genética , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/genética , Neovascularización Patológica/genética , ARN Largo no Codificante/metabolismo , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Hepatoblastoma/patología , Humanos , Neoplasias Hepáticas/patología , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica , ARN Largo no Codificante/genética , Regulación hacia Arriba/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Hepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. PATIENTS AND METHODS: Twelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. RESULT: There were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. CONCLUSION: Early inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy.
Asunto(s)
Arteria Hepática/cirugía , Hepatoblastoma/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Donadores Vivos , Vena Porta/cirugía , Niño , Preescolar , Femenino , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/mortalidad , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/mortalidad , Masculino , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: Hepatoblastoma (HB) is a rare childhood tumor. We investigated the effect of intraoperative management of the intrahepatic major vessels in children with HB. METHODS: Between April 2005 and August 2012, surgical resection was performed on 50 children with hepatoblastoma. These children were divided into a vessel-ligation group (n = 20) and a vessel-repair group (n = 30). In the vessel-ligation group, the intrahepatic major vessels were ligated and removed together with the tumor and the affected liver lobe/liver parenchyma. In the vessel-repair group, the affected intrahepatic major vessels were dissected and preserved as much as possible and the normal liver lobe/liver parenchyma and blood supply from these vessels were also preserved. The outcomes were analyzed by postoperative follow-up. RESULTS: In the vessel-ligation group, two patients gave up surgery, six patients underwent palliative resection, and 12 patients underwent en bloc resection; four patients died of liver failure and eight patients fully recovered and were discharged. In the vessel-repair group, all 30 patients underwent en bloc resection and were discharged after satisfactory healing. After a follow-up time of 5 - 36 months (median: 20 months), two patient in the vessel-ligation group survived and 22 patients in the vessel-repair group survived. CONCLUSIONS: Patients with HB can be successfully treated by tumor resection with vascular repair. This method prevents postoperative liver failure, ensures patient safety during the perioperative period, and allows for early chemotherapy.
Asunto(s)
Hepatoblastoma/cirugía , Neoplasias Hepáticas/cirugía , Niño , Preescolar , Femenino , Estudios de Seguimiento , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/patología , Humanos , Lactante , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Masculino , Estadificación de NeoplasiasRESUMEN
Hepatoblastoma is a pediatric malignancy characterized by the uncontrolled proliferation of immature hepatocytes (hepatoblasts). This disease is diagnosed primarily in children younger than 5 years and is disproportionately observed in former premature infants. Cytogenetically, hepatoblastoma is characterized by numerical aberrations, as well as unbalanced translocations involving the proximal region of chromosome 1q. The NOTCH2 gene has been mapped to this locus, and it is well established that the NOTCH gene family is an important regulator of several developmental pathways. Specifically, the NOTCH2 protein is known to delay hepatoblast maturation during early hepatic organogenesis, and the reduction of NOTCH2 expression correlates with the differentiation of hepatoblasts into hepatocytes and biliary cells in the developing liver. We hypothesized that NOTCH2 is involved in the pathogenesis of hepatoblastoma by maintaining a population of undifferentiated hepatoblasts. We studied the immunohistochemical expression of NOTCH2 and its isoforms NOTCH1, NOTCH3, and NOTCH4 and the NOTCH2 primary ligand JAGGED1 in hepatoblastomas. Compared with the normal liver, an increased level of NOTCH2 expression was seen in 22 of 24 (92%) hepatoblastomas. There was no significant staining for other NOTCH isoforms and JAGGED1 in hepatoblastomas. Therefore, we suggest that NOTCH2 expression and activation, independent of JAGGED1 expression, may contribute to the pathogenesis of hepatoblastoma. In the hepatoblastoma sinusoidal vasculature, we saw NOTCH3 and NOTCH1 expression. These observations have potential implications with regard to therapeutic targeting of the NOTCH signaling pathway in hepatoblastomas.
Asunto(s)
Hepatoblastoma/metabolismo , Hepatocitos/metabolismo , Neoplasias Hepáticas/metabolismo , Receptor Notch2/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas de Unión al Calcio/metabolismo , Diferenciación Celular , Núcleo Celular/metabolismo , Núcleo Celular/patología , Proliferación Celular , Niño , Preescolar , Citoplasma/metabolismo , Citoplasma/patología , Femenino , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/patología , Hepatocitos/patología , Humanos , Inmunohistoquímica/métodos , Lactante , Recién Nacido , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteína Jagged-1 , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Masculino , Proteínas de la Membrana/metabolismo , Proteínas Serrate-Jagged , Transducción de SeñalRESUMEN
Vascular endothelial growth factor (VEGF) blockade has been validated clinically as a treatment for human cancers, yet virtually all patients eventually develop progressive disease during therapy. In order to dissect this phenomenon, we examined the effect of sustained VEGF blockade in a model of advanced pediatric cancer. Treatment of late-stage hepatoblastoma xenografts resulted in the initial collapse of the vasculature and significant tumor regression. However, during sustained treatment, vessels recovered, concurrent with a striking increase in tumor expression of perlecan, a heparan sulfate proteoglycan. Whereas VEGF mRNA was expressed at the periphery of surviving clusters of tumor cells, both secreted VEGF and perlecan accumulated circumferential to central vessels. Vascular expression of heparanase, VEGF receptor-2 ligand binding, and receptor activation were concurrently maintained despite circulating unbound VEGF Trap. Endothelial survival signaling via Akt persisted. These findings provide a novel mechanism for vascular survival during sustained VEGF blockade and indicate a role for extracellular matrix molecules that sequester and release biologically active VEGF.
Asunto(s)
Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Colágeno/metabolismo , Células Endoteliales/enzimología , Células Endoteliales/metabolismo , Activación Enzimática , Femenino , Regulación Neoplásica de la Expresión Génica , Glucuronidasa/metabolismo , Proteoglicanos de Heparán Sulfato/metabolismo , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/enzimología , Hepatoblastoma/genética , Hepatoblastoma/patología , Humanos , Ratones , Ratones Desnudos , Modelos Biológicos , Estadificación de Neoplasias , Neoplasias/irrigación sanguínea , Neoplasias/enzimología , Neoplasias/patología , Neovascularización Patológica/genética , Fosforilación , Unión Proteica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Inducción de Remisión , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Hypoxia-inducible factor-1 (HIF-1) has a central role in cellular responses to hypoxia, including the transcriptional activation of a number of genes involved in angiogenesis in tumors. We found that curcumin, a natural, biologically active compound isolated from the commonly used spice turmeric, significantly decreases hypoxia-induced HIF-1alpha protein levels in HepG2 hepatocellular carcinoma cells. Moreover, curcumin suppressed the transcriptional activity of HIF-1 under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major HIF-1 target angiogenic factor. Curcumin also blocked hypoxia-stimulated angiogenesis in vitro and down-regulated HIF-1alpha and VEGF expression in vascular endothelial cells. These findings suggest that curcumin may play pivotal roles in tumor suppression via the inhibition of HIF-1alpha-mediated angiogenesis.
Asunto(s)
Curcumina/farmacología , Hepatoblastoma/irrigación sanguínea , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Hepáticas/irrigación sanguínea , Procesos de Crecimiento Celular/efectos de los fármacos , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/fisiología , Regulación hacia Abajo/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Hepatoblastoma/tratamiento farmacológico , Hepatoblastoma/genética , Hepatoblastoma/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Activación Transcripcional/efectos de los fármacos , Transfección , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and microvascular density (MVD) count in pediatric malignant liver tumor and their clinical significances. METHODS: Fourteen children with malignant liver tumors including seven hepatocellular carcinomas (HCCs), five hepatoblastomas, one malignant mesenchymoma and one rhabdomyosarcoma were studied. Twelve adult HCC samples served as control group. All samples were examined with streptavidin-biotin peroxidase (SP) immunohistochemical staining for VEGF expression and MVD count. RESULTS: VEGF positive expression in all pediatric malignant liver tumors was significantly higher than that in adult HCC (0.4971+/-0.14 vs 0.4027+/-0.03, P<0.05). VEGF expression in pediatric HCC group was also markedly higher than that in adult HCC group (0.5665+/-0.10 vs 0.4027+/-0.03, P<0.01) and pediatric non-HCC group (0.5665+/-0.10 vs 0.4276+/-0.15, P<0.05). The mean value of MVD in pediatric malignant liver tumors was significantly higher than that in adult HCC (33.66+/-12.24 vs 26.52+/-4.38, P<0.05). Furthermore, MVD in pediatric HCC group was significantly higher compared to that in adult HCC group (36.94+/-9.28 vs 26.52+/-4.38, P<0.05), but there was no significant difference compared to the pediatric non-HCC group (36.94+/-9.28 vs 30.37+/-14.61, P>0.05). All 7 children in HCC group died within 2 years, whereas the prognosis in pediatric non-HCC group was better, in which two patients survived more than 5 years. CONCLUSION: Children with malignant liver tumors, especially with HCC, may have extensive angiogenesis that induces a rapid tumor growth and leads to a poor prognosis.
Asunto(s)
Carcinoma Hepatocelular/irrigación sanguínea , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Neovascularización Patológica/patología , Adolescente , Carcinoma Hepatocelular/mortalidad , Niño , Preescolar , Femenino , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/mortalidad , Hepatoblastoma/patología , Humanos , Lactante , Neoplasias Hepáticas/mortalidad , Masculino , Mesenquimoma/irrigación sanguínea , Mesenquimoma/mortalidad , Mesenquimoma/patología , Microcirculación , Neovascularización Patológica/metabolismo , Neovascularización Patológica/mortalidad , Pronóstico , Rabdomiosarcoma/irrigación sanguínea , Rabdomiosarcoma/mortalidad , Rabdomiosarcoma/patología , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To study the expressions and activities of Rho GTPases in hypoxia and its relationship with tumor angiogenesis. METHODS: Three tumor cell lines were used in this study: gastric cancer cell lines AGS, SGC7901 and hepatocellular carcinoma cell line HepG2. Expression level of Rac1 mRNA was detected by semi-quantitative RT-PCR. Activity of Rac1 was determined by pull-down assay and expression of HIF-1alpha, VEGF, p53 and PTEN protein was detected by Westernblot. RESULTS: The expression level of Rac1 mRNA was significantly increased in hypoxia compared to normoxia. Pull-down assay showed that hypoxia-induced activity of Rac1 was elevated in a time-dependent manner and climaxed at 3 hours. The expressions of HIF-1alpha and VEGF protein were up-regulated, while those of PTEN and p53 protein were down-regulated. CONCLUSION: These results indicate that hypoxia enhances Rac1 expression which might be involved in tumor angiogenesis by reacting with hypoxia-responsive genes.
Asunto(s)
Hepatoblastoma/metabolismo , Neoplasias Hepáticas/metabolismo , Neovascularización Patológica , Neoplasias Gástricas/metabolismo , Proteína de Unión al GTP rac1/biosíntesis , Proteínas de Unión al GTP rho/biosíntesis , Hipoxia de la Célula , Línea Celular Tumoral , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/patología , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/patología , Fosfohidrolasa PTEN/biosíntesis , Fosfohidrolasa PTEN/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Neoplasias Gástricas/irrigación sanguínea , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genética , Proteína de Unión al GTP rac1/genética , Proteínas de Unión al GTP rho/genéticaRESUMEN
Until now surgical resection was still considered as the only choice of successful treatment of hepatoblastoma. Therefore, successful use of transcatheter arterial chemoembolization (TACE) alone to cure the unresectable hepatoblastoma in an infant was firstly reported. A 6-month-old boy presented with a huge abdominal mass and was found to have a hepatoblastoma of 17.5 cm x 11.5 cm x 10 cm on computed tomography (CT) scan. The serum alpha-fetoprotein (AFP) was elevated to 6250 ng/mL. On the first TACE the main feeding arteries were completely occluded by stainless steel embolization coils. After one month tumor shrinkage was 75%, but a newly formed feeding artery was found and embolized on second TACE. Since the third TACE no newly formed feeding artery was found and 6 courses of intravenous chemotherapy were consolidated. On the last DSA and CT the tumor was completely disappeared and AFP returned to normal. During the follow-up he remained disease-free for 33 months until the present report. TACE may provide an additional promising choice in the treatment of hepatoblastoma.
Asunto(s)
Quimioembolización Terapéutica/métodos , Hepatoblastoma/terapia , Angiografía , Diagnóstico por Imagen , Supervivencia sin Enfermedad , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/patología , Humanos , Lactante , Masculino , Arteria Mesentérica Superior , Resultado del TratamientoRESUMEN
BACKGROUND: Hepatoblastoma is the most common primary hepatic malignancy of childhood, frequently presenting as advanced disease. Vascular endothelial growth factor (VEGF) is an endothelial mitogen and survival factor critical to growth and angiogenesis in many human cancers. Inhibition of VEGF effectively suppresses tumorigenesis in multiple experimental models. The authors hypothesized that anti-VEGF antibody would alter vascular architecture and impede tumor growth in experimental hepatoblastoma. METHODS: The Institutional Animal Care and Use Committee of Columbia University approved all protocols. Xenografts were established in athymic mice by intrarenal injection of cultured human hepatoblastoma cells. Anti-VEGF antibody (100 microg/dose) or vehicle was administered intraperitoneally 2 times per week for 5 weeks. At week 6, 10 control/treated mice were killed and remaining animals maintained without treatment until week 8. Tumor weights were compared by Kruskal-Wallis analysis, and vascular alterations ascertained by fluorescein angiography and specific immunostaining. RESULTS: Anti-VEGF antibody significantly inhibited tumor growth at 6 weeks (1.85 g +/- 0.60 control, 0.05 +/- 0.03 antibody, P <.0003). In comparison with controls, treated xenografts showed decreased vascularity and dilated surviving vessels with prominent vascular smooth muscle elements. CONCLUSIONS: Specific anti-VEGF therapy inhibits neoangiogenesis and significantly suppresses tumor growth in experimental hepatoblastoma. Surviving vasculature displays dilation and increased vascular smooth muscle. Anti-VEGF agents may represent new therapeutic alternatives for children with advanced disease.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Factores de Crecimiento Endotelial/antagonistas & inhibidores , Hepatoblastoma/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Linfocinas/antagonistas & inhibidores , Proteínas de Neoplasias/antagonistas & inhibidores , Neovascularización Patológica/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Factores de Crecimiento Endotelial/inmunología , Femenino , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/secundario , Humanos , Péptidos y Proteínas de Señalización Intercelular/inmunología , Neoplasias Hepáticas/irrigación sanguínea , Linfocinas/inmunología , Ratones , Ratones Desnudos , Proteínas de Neoplasias/inmunología , Trasplante de Neoplasias , Neoplasias Peritoneales/secundario , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Advanced hepatoblastoma often is lethal despite current therapies, yet development of novel approaches has been hampered by the lack of biologically relevant models. One new strategy selectively targets endothelium rather than tumor cells using frequently administered, low-dose ("metronome") chemotherapy. Metronome topotecan has antiangiogenic activity in some experimental tumors. The authors developed a xenograft model of human hepatoblastoma to test the effect of metronome topotecan in this system. METHODS: Xenografts resulted from intrarenal injection of cultured human hepatoblastoma cells in athymic mice. Topotecan (0.36 mg/kg/dose) or vehicle was injected intraperitoneally 5 times per week. At week 6, 10 control/treated mice were killed, and remaining animals were maintained without treatment until week 8. Tumor weights were compared by Kruskal-Wallis analysis, and vascular alterations were ascertained by specific immunostaining. RESULTS: Metronome topotecan affected tumor weights in a delayed fashion: weights were diminished significantly only at 8 weeks (treated v control: 6 weeks, 0.59 g v 82 g, P value, not significant; 8 weeks, 1.13 g v 3.82; P <.02). Decreased vascularity and increased endothelial cell apoptosis were observed in treated xenografts. CONCLUSIONS: Metronome topotecan inhibits growth and neovascularization in experimental hepatoblastoma. The durability of this effect is novel and has not been observed in other xenograft tumor models. Cytotoxic targeting of endothelial cells may hold particular promise for therapy of children with advanced hepatoblastoma. .
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Hepatoblastoma/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Topotecan/farmacología , Animales , Femenino , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/patología , Humanos , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/fisiopatología , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Neovascularización Patológica/patología , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
We present a case of pulmonary embolism that occurred during the injection of lipiodol during transcatheter arterial chemoembolization under general anaesthesia. A 7-year-old child suffering from a large hepatoblastoma was admitted for arterial chemoembolization and carcinostatic administration. Pulmonary embolism due to lipiodol during arterial chemoembolization was evident by a sudden fall in oxyhaemoglobin saturation from 100 to 90%. This was associated with a spread of lipiodol into both lungs, particularly the middle lung zones and detected by chest fluoroscopy. Arterial blood gases returned to normal values 1 day later but pulmonary infiltration persisted for 7 days before final clearance. Pulmonary embolism caused by lipiodol during arterial chemoembolization is infrequent, but such a complication could prove fatal. Understanding the risk of pulmonary embolism in patients receiving lipiodol, during and after arterial chemoembolization, and late onset pulmonary injury is important and a close follow-up for several days after arterial chemoembolization is advisable.
Asunto(s)
Quimioembolización Terapéutica/efectos adversos , Medios de Contraste/efectos adversos , Doxorrubicina/análogos & derivados , Hepatoblastoma/terapia , Aceite Yodado/efectos adversos , Neoplasias Hepáticas/terapia , Embolia Pulmonar/etiología , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Cateterismo Periférico , Niño , Cuidados Críticos , Doxorrubicina/administración & dosificación , Fluoroscopía , Estudios de Seguimiento , Hepatoblastoma/irrigación sanguínea , Humanos , Neoplasias Hepáticas/irrigación sanguínea , Masculino , Oxígeno/sangre , Oxihemoglobinas/análisis , Respiración con Presión Positiva , Radiografía IntervencionalRESUMEN
We used contrast-enhanced three-dimensional magnetic resonance angiography (3D MRA) modified for pediatric use to evaluate the hepatic vasculature prior to partial hepatectomy in five consecutive children with hepatoblastoma. Modifications included non-breath-hold technique in four of the five children who were sedated. The single breath-hold technique was performed in only one awake child. Scan delay times were based on contrast infusion time rather than total infusion time. The hepatic artery, portal vein, and inferior vena cava were identified in all patients. MRA findings were confirmed by conventional angiography in one patient and by surgery in all. Contrast-enhanced 3D MRA is a useful and rapid technique prior to partial hepatectomy in patients with hepatoblastoma.
Asunto(s)
Hepatoblastoma/irrigación sanguínea , Neoplasias Hepáticas/irrigación sanguínea , Hígado/irrigación sanguínea , Angiografía por Resonancia Magnética/métodos , Niño , Preescolar , Femenino , Gadolinio , Hepatectomía , Hepatoblastoma/cirugía , Humanos , Aumento de la Imagen , Neoplasias Hepáticas/cirugía , MasculinoRESUMEN
Although surgical treatment with resection for spontaneous rupture of hepatoblastoma into the free abdominal cavity is difficult in small children, it may be the only treatment available. The authors describe a 16-month-old girl who showed a progressive decrease in hematocrit and no response to blood transfusion, after spontaneous rupture of a large hepatoblastoma that extended to the pubic bone. Percutaneous transcatheter arterial embolization could not be performed because selective catheterization was impossible. Therefore, emergency surgery was conducted. After intraoperative transcatheter arterial embolization (IOTAE) to control hemorrhage, left trisegmentectomy was performed. The patient then underwent chemotherapy, followed by autologous bone marrow transplantation. The hemorrhage from the ruptured tumor was completely arrested by IOTAE, and the postoperative course was uneventful. Hepatic resection after IOTAE, followed by chemotherapy and bone marrow transplantation, represents a promising treatment for ruptured hepatoblastoma.
Asunto(s)
Embolización Terapéutica/métodos , Hemoperitoneo/cirugía , Hepatectomía/métodos , Hepatoblastoma/cirugía , Neoplasias Hepáticas/cirugía , Angiografía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Terapia Combinada , Doxorrubicina/administración & dosificación , Femenino , Hemoperitoneo/diagnóstico por imagen , Arteria Hepática/diagnóstico por imagen , Hepatoblastoma/irrigación sanguínea , Hepatoblastoma/tratamiento farmacológico , Humanos , Lactante , Neoplasias Hepáticas/irrigación sanguínea , Neoplasias Hepáticas/tratamiento farmacológico , Rotura Espontánea , Tomografía Computarizada por Rayos XRESUMEN
Sinusoids are found not only in the normal liver but also in certain liver tumours, including hepatoblastoma, the most common malignant liver tumour in childhood. In this study, sinusoids in 12 hepatoblastomas, of various subtypes, and in normal liver were investigated with UEA-1 and antibodies against von Willebrand's factor, CD31 and CD34 to detect differences of possible diagnostic significance. In the normal liver, staining of sinusoids was seen with all these markers, but it was focal and confined to a few sinusoids near the portal tracts. In hepatoblastoma, the endothelial markers reacted with the sinusoids to varying extents. UEA-1 and anti-CD34 usually stained the majority of these vessels, anti-CD34 staining greater numbers of sinusoids and with greater intensity. Immunostaining revealed that both number and spatial organization of sinusoids in hepatoblastoma are dependent on the subtype. In addition to staining of endothelium, one of the two small cell hepatoblastomas exhibited strong immunoreactivity of the tumour cells for CD34. These findings show that the marked difference in sinusoidal immunoreactivity for CD34 between normal liver and hepatoblastoma could be useful for discriminating between non-neoplastic liver tissue and highly differentiated fetal hepatoblastoma. Our findings also show that small cell hepatoblastoma, in addition to acute leukaemia, should be considered when immunoreactivity for CD34 is found in small round and blue cell tumours in childhood.