Metástases pulmonares em crianças: estamos operando desnecessariamente? / Pulmonary metastases in children: are we operating unnecessarily?

RESUMO Objetivo: determinar, em pacientes pediátricos portadores de neoplasias malignas, as características de nódulos pulmonares identificados à tomografia computadorizada, capazes de diferenciar nódulos benignos de metástases. Métodos: estudo retrospectivo de pacientes submetidos a ressecções pulmonares de nódulos diagnosticados como metástases em um período de sete anos. Achados de tomografia e da cirurgia, assim como resultados dos exames anatomopatológicos foram comparados. Resultados: nove pacientes, submetidos a 11 intervenções cirúrgicas, foram estudados. Entre as variáveis estudadas, apenas o tamanho do nódulo, maior do que 12,5mm provou ser estatisticamente significante para predizer malignidade. Conclusão: esse estudo sugere que, entre as características tomográficas de nódulos pulmonares de crianças portadoras de neoplasias malignas, apenas o tamanho da lesão foi preditor de malignidade.

ABSTRACT Objective: to determine, in pediatric patients with malignant neoplasms, the characteristics of pulmonary nodules identified on computed tomography, as well as the possibility of differentiating benign lesions from metastases. Methods: we conducted a retrospective study of patients submitted to pulmonary resections of nodules diagnosed as metastases in a period of seven years. We compared computed tomography and surgery findings, as well as results of anatomopathological examinations. Results: we studied nine patients submitted to 11 surgical interventions. Among the studied variables, only nodule size greater than 12.5mm proved to be statistically significant to predict malignancy. Conclusion: among the tomographic characteristics of pulmonary nodules in children with malignant neoplasms, only the size of the lesion was a predictor of malignancy.

New concepts and outcomes for children with hepatoblastoma based on the experience of a tertiary center over the last 21 years

OBJECTIVE: The aim of this study was to summarize the experience of a tertiary center in treating hepatoblastoma for the last 21 years. PATIENTS AND METHODS: Fifty-eight cases were included. The tumor extent and prognosis were assessed using the PRETEXT system. The following data were analyzed: age at diagnosis, comorbidities, prematurity, treatment modalities, histopathological findings, surgical details and complications, treatment outcomes, chemotherapy schedules, side effects and complications. Treatment outcomes included the occurrence of local or distant recurrence, the duration of survival and the cause of death. The investigation methods were ultrasonography, CT scan, serum alpha-fetoprotein level measurement and needle biopsy. Chemotherapy was then planned, and the resectability of the tumor was reevaluated via another CT scan. RESULTS: The mean numbers of neoadjuvant cycles and postoperative cycles of chemotherapy were 6±2 and 1.5±1.7, respectively. All children except one were submitted for surgical resection, including 50 partial liver resections and 7 liver transplantations. Statistical comparisons demonstrated that long-term survival was associated with the absence of metastasis (p=0.04) and the type of surgery (resection resulted in a better outcome than transplantation) (p=0.009). No associations were found between vascular invasion, incomplete resection, histological subtype, multicentricity and survival. The overall 5-year survival rate of the operated cases was 87.7%. CONCLUSION: In conclusion, the experience of a Brazilian tertiary center in the management of hepatoblastoma in children demonstrates that long survival is associated with the absence of metastasis and the type of surgery. A multidisciplinary treatment involving chemotherapy, surgical resection and liver transplantation (including transplantations using tissue from living donors) led to good outcomes and survival indexes. .

Liver cancer stem cells are selectively enriched by low-dose cisplatin

Accumulating evidence has indicated the importance of cancer stem cells in carcinogenesis. The goal of the present study was to determine the effect of low-dose cisplatin on enriched liver cancer stem cells (LCSCs). Human hepatoblastoma HepG2 cells were treated with concentrations of cisplatin ranging from 1 to 5 μg/mL. Cell survival and proliferation were evaluated using a tetrazolium dye (MTT) assay. LCSCs were identified using specific markers, namely aldehyde dehydrogenase-1 (ALDH1) and CD133. The percentage of ALDH1+ or CD133+ cells was examined by flow cytometric analysis. The expression of ALDH1 and/or CD133 in HepG2 cells was determined by immunocytochemical analysis. Low-dose cisplatin treatment significantly decreased cell survival in HepG2 cells after 24 or 72 h. However, the percentage of LCSCs in the surviving cells was greatly increased. The percentage of ALDH1+ or CD133+ cells was increased in a time- and dose-dependent manner after treatment with 1-4 μg/mL cisplatin, whereas 5 μg/mL cisplatin exposure slightly reduced the number of positive cells. These findings indicate that low-dose cisplatin treatment may efficiently enrich the LCSC population in HepG2 cells.

Lesiones focales hepáticas en niños / Focal liver lesions in children

Las lesiones focales del hígado comprenden un grupo heterogéneo de entidades como tumores benignos y malignos, sólidos o quistes, vasculares, masas inflamatorias y metástasis, entre otras. Reportar lesiones focales hepáticas en niños, características clínicas, estudios por imágenes y conducta terapéutica. Estudio descriptivo, retrospectivo, basado en la revisión de 16 historias clínicas de niños con lesiones focales hepáticas en el periodo comprendido entre enero 2007 a enero 2012. Se excluyeron los abscesos hepáticos. El 68,75%11 eran del sexo masculino y 31,25%5 del sexo femenino; con edad promedio de 9,5 años (rango: 10 días - 14 años). Las lesiones focales benignas fueron: hemangioma 4/16 (25%), hematoma hepático 4/16 (25%), quiste hepático 3/16 (18,75%), hiperplasia nodular focal 1/16 (6,25%) adenoma 1/16 (6,25%) y las malignas: hepatocarcinoma 2/16 (12,50%) y hepatoblastoma 1/16 (6,25%). La mayoría de los pacientes (56,25%) se encontraban asintomáticos, 3/16 (18,75%) presentaron dolor abdominal, 3/16 (18,75%) masa palpable y 2/16 (12,5%) ictericia. La lesión fue identificada por ultrasonido abdominal en todos los pacientes y sólo el 56,25% (9/16) ameritaron tomografía con contraste. Al 43,75% (7/16) se les realizó marcadores tumorales y de estos el 42,85% (3/7) reportaron neoplasias. El funcionalismo hepático reportó normal en el 75% de los casos. El ultrasonido abdominal es el método de elección para el diagnóstico y seguimiento de las lesiones focales hepáticas, mientras el origen de las mismas, guía la conducta terapéutica

Focal liver lesions comprise a heterogeneous group of entities such as benign and malignant, solid or cysts, vascular, inflammatory masses and metastasis among others. To report focal liver lesions in children, clinical features, imaging and therapeutic behavior. A descriptive, retrospective study based on a review of 16 case histories of children with focal liver lesions in the period from January 2007 to January 2012. Liver abscesses were excluded. 68.75%11 were male and 31.25%5 females, mean age 9.5 years (range: 10 days - 14 years). Focal lesions were benign: Hemangioma 4/16 (25%), liver hematoma 4/16 (25%), hepatic cyst 3/16 (18.75%), nodular focal hyperplasia 1/16 (6.25%) and adenomas 1/16 (6.25%) and malignant: Hepatocellular carcinoma 2/16 (12.50%) and hepatoblastoma 1/16 (6.25%). Most patients (56.25%) were asymptomatic, 3/16 (18.75%) had abdominal pain, 3/16 (18.75%) and palpable mass 2/16 (12.5%) jaundice. The lesion was identified by abdominal ultrasound in all patients and only 56.25% (9/16) needed tomography with contrast. To 43.75% (7/16) underwent tumor markers and of these 42.85% (3/7) reported neoplasm. Normal hepatic function reported in 75% of cases. An abdominal ultrasound is the method of choice for the diagnosis and management of focal liver lesions, while the origin of them, guide therapeutic conduct

Hepatoblastoma: Experience from a single center.

Background: The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability. Aims: We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs. Settings and Design: Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004. Materials and Methods: Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed. Results: There were 9 boys and 3 girls, aged 5-60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications. Conclusions: Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy.

Hepatoblastoma en el recien nacido: reporte de un caso / Hepatoblastoma in newborn: a case report

El hepatoblastoma en el recién nacido tiene una baja incidencia, sin embargo es el tumor hepático maligno más común. Solo un 4 por ciento se diagnostica al momento del nacimiento y es muy raro el diagnóstico prenatal. El hepatoblastoma se asocia a malformaciones o condiciones genéticas como el síndrome de Beckwith-Wiedemann, también con el muy bajo peso al nacer. La quimioterapia preoperatoria mejora las posibilidades de resección y trasplante, así como se reporta mejoría de la sobrevida de un 40 por ciento a un 90 por ciento. Se describe el caso de un recién nacido con un hepatoblastoma de tipo epitelial, en estadio IV dada la imposibilidad de resección primaria.

Infecciones asociadas a catéteres vasculares de larga permanencia en pacientes pediátricos con cáncer / Infections associated to vascular catheters of long permanency in patient pediatric with cancer

La disponibilidad de catéteres intravasculares permanentes para manejo de pacientes pediátricos con cáncer facilita el tratamiento quimioterápico y disminuye la morbilidad; sin embargo, las infecciones asociadas constituyen una causa importante de bacteremia nosocomial. Conocer la incidencia de infecciones asociadas a catéteres vasculares de larga permanencia en pacientes pediátricos oncológicos. Estudio descriptivo, petrospectivo y transversal mediante el cual se determinó la frecuencia de infecciones asociadas a catéteres en pacientes pediátricos con cáncer hospitalizados en el Servicio de Oncología del Hospital "J.M de Los Ríos", evaluados por infectología, entre enero de 2000 y diciembre de 2004. Se determinó la relación entre tipo de catéter (con o sin reservorio) y factores como frecuencia de infección, nivel socioeconómico, tiempo entre implantación e infección, tipo de infección, microorganismos involucrados y permanencia hospitalaria. Se implantaron 24 catéteres en 16 pacientes: 5 con reservorio y 19 sin reservorio. Se presentó un episodio de infección (candidemia) en los pacientes con catéteres con reservorio, mientras que hubo 11 infecciones en los otros (7 bacteriemias, 1 candidemia, 2 infecciones en sitio de implantación y 1 infección combinada), aislándose principalmente bacterias gramnegativas y Candida sp.). Todos presentaron fiebre. Las infecciones ocurrieron en 12/16 pacientes con condiciones socioeconómicas menos favorables. El lapso entre implantación e infección fue variable. Las infecciones asociadas a catéteres vasculares son menos frecuentes en aquellos con reservorio. La bacteremia fue el tipo de infección más reportada. Los microorganismos gramnegativos fueron los más involucrados. El 50 por ciento de los pacientes estuvo hospitalizado menos de 33 días.

Teratoid Hepatoblastoma: Multidirectional Differentiation of Stem Cell of the Liver

Hepatoblastoma is the most common malignant hepatic neoplasm of childhood, showing a wide spectrum of epithelial and mesenchymal components. Teratoid hepatoblastoma, which reveals multiple lines of tissue differentiation such as mucinous epithelium, melanin pigment, endocrine differentiation, glial and mesenchymal components, has rarely been observed. We report a case of teratoid hepatoblastoma in a 22-month-old girl. She had been diagnosed with hepatoblastoma through percutaneous needle biopsy of the liver and treated with 10 chemotherapy cycles of epirubicin, VP-16 and cisplatin and with hepatic artery embolization. After 10 months, an extended left lobectomy was performed. Grossly, a multinodular, partly well-demarcated, solid mass (7 x 5 cm) with dense fibrosis and focal cystic change occupied almost the entire specimen. There was extensive necrosis due to preoperative treatment. Microscopically, the tumor showed multiple lines of differentiation, which was composed of embryonal, fetal hepatocytes and mesenchymal elements with numerous foci of osteoid. There were also other components showing endodermal, neural, melanocytic and endocrine differentiation. These teratoid components were considered relatively resistant to preoperative chemotherapy, in contrast to extensive necrosis of both embryonal and fetal hepatocytes. These teratoid features of hepatoblastoma are considered to be a multidirectional differentiation of the small epithelial cells or stem cells of the tumor.

Manejo multidisciplinario de tumores hepáticos malignos en el niño: una experiencia nacional reciente / Multidisciplinary management of hepatic malignant tumors in children: report of 6 cases

Background: malignant hepatic tumors (Mht) are rare in children. Among them hepatoblastoma (HB) is the most common. Aim: to report the results of the multidisciplinary management in 6 consecutive children: five HB and one metastatic Wilms tumor (MWT). Patients and methods: the mean age of patients was 42 months. All HB patients had elevated serum alfafetoprotein (median 150,000 ng/ml). All patients received preoperative chemotherapy: HB patients received carboplatin/doxorrubicin alternating with cisplatin, and the MWT patient, vincristine alone. Surgery included two formal right and two formal left hepatectomies, one extensive central resection with partial left segmentectomy, and one lateral segmentectomy. Extracorporeal circulation was used in the child with atrial involvement. All patients received postoperative chemotherapy. Results: all tumors had variable regresion on preoperative chemotherapy. Complete resection with negative margins was achieved in all patients. The degree of tumor necrosis on histology ranged from 60 percent to 90 percent. Alfafetoprotein levels fell to under 10 ng/ml in all HB cases, one to three months after surgery. All patients survive free of disease at a median follow up of 19 months. Conclusion: a multidisciplinary approach including the well timed used of chemotherapy and surgery is highly effective in the management of pediatric malignant tumors

Role of Ca2+ influx in the tert-butyl hydroperoxide-induced apoptosis of HepG2 human hepatoblastoma cellse

Oxidative stress appears to be implicated in the pathogenesis of various diseases including alcoholic liver injury. In this study we investigated the mechanism of apoptosis induced by tert-butyl hydroperoxide (TBHP) in HepG2 human hepatoblastoma cells. Treatment with TBHP significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity, indicating that TBHP induced oxidative stress in the HepG2 cells. TBHP also induced reduction of cell viability and DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. In addition, TBHP induced a sustained increase in intracellular Ca2+ concentration, which was completely prevented by the extracellular Ca2+ chelation with EGTA. TBHP also induced Mn2+ influx. These results indicate that the intracellular Ca2+ increase by TBHP is exclusively due to Ca2+ influx from the extracellular site. Treatment with either an extracellular (EGTA) or an intracellular Ca2+ chelator (BAPTA/AM) significantly suppressed the TBHP-induced apoptosis. Taken together, these results suggest that TBHP induced the apoptotic cell death in the HepG2 cells and that Ca2+ influx may play an important role in the apoptosis induced by TBHP.

Comparación de la biopsia por aspiración con aguja fina y la biopsia quirúrgica en el diagnóstico de tumores en niños / Comparison between diagnosisi by fine needle aspiration biopsy and conventional biopsy in children's tumors

Introducción. La biopsia por aspiración con aguja fina (BAAF) es un método de diagnóstico útil, inocuo y rápido para el estudio inicial de los tumores superficiales y profundos que ha sido utilizado cada vez con mayor frecuencia en niños. Fue propósito de este trabajo evaluar la precisión diagnóstica del procedimiento en el diagnóstico inicial de tumores en niños. Material y métodos. Se revisaron todas las BAAF diagnosticadas en un período de 24 meses y se seleccionaron aquellas con diagnóstico de tumor o masa tumoral que tuvieran además estudio histopatológico subsecuente ya sea mediante biopsia o extirpación total de la lesión. Se compararon los diagnósticos de ambos procedimientos y se juzgó conveniente calcular la sensibilidad y especificidad. Resultados. De 89 BAAF registradas en el período de estudio solamente 34 tuvieron estudio histopatológico subsecuente. La gran mayoría de las lesiones correspondieron a neoplasias malignas. En 30 casos el diagnóstico de la BAAF estuvo de aucerdo con el de la biopsia quirúrgica y no hubo acuerdo en 4. La sensibilidad del método fue del 97 por ciento y la especificidad del 33 por ciento. Conclusiones. Los resultados de este estudio indican que la BAAF es confiable para el diagnóstico inicial de tumores superficiales y profundos en niños

Inhibition of HBV replication by antisense oligodeoxyribonucleotides in HepG2 cells transfected with a cloned HBV DNA

The effect of antisense oligodeoxyribonucleotides(oligo[dN]s) on hepatitis B virus(HBV) replication in HepG2 cells harboring a cloned HBV genome was examined. Antisense oligo(dN)s directed at translational initiation sites of S, pre C and P genes of HBV were treated to the cells and the amount of HBsAg and HBV DNA content were measured 72 hours after the treatment. HBsAg expressions in HepG2 cells harboring the HBV genome were inhibited 68%, 53%, and 46% by the treatment with antisense oligo[dN] directed at S, pre C, and P gene loci, respectively, and HBV DNA content in the cells was also reduced by the treatment of each antisense oligo[dN]. The doubling times of the cultured cells treated with 25 micrograms, 50 micrograms, and 100 micrograms of antisense oligo[dN]/ml medium were 43.3, 62.1, and 93.0 hours, respectively, compared with 37.5 hours of the untreated control cells. Cellular DNA synthesis was inhibited by the treatment with 100 micrograms/ml of antisense oligo [dN], however, no significant effect was observed by the treatment with 50 micrograms or less of antisense oligo[dN]/ml. These results suggested that antisense oligo[dN]s specific to the translational initiation sites of S, pre C, and P genes of HBV may have therapeutic potential for the suppression of HBV propagation in chronic HBV infected patients.