Prognostic value of patient-derived xenograft engraftment in pediatric sarcomas.

The goals of this work were to identify factors favoring patient-derived xenograft (PDX) engraftment and study the association between PDX engraftment and prognosis in pediatric patients with Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma. We used immunodeficient mice to establish 30 subcutaneous PDX from patient tumor biopsies, with a successful engraftment rate of 44%. Age greater than 12 years and relapsed disease were patient factors associated with higher engraftment rate. Tumor type and biopsy location did not associate with engraftment. PDX models retained histology markers and most chromosomal aberrations of patient samples during successive passages in mice. Model treatment with irinotecan resulted in significant activity in 20 of the PDXs and replicated the response of rhabdomyosarcoma patients. Successive generations of PDXs responded similarly to irinotecan, demonstrating functional stability of these models. Importantly, out of 68 tumor samples from 51 patients with a median follow-up of 21.2 months, PDX engraftment from newly diagnosed patients was a prognostic factor significantly associated with poor outcome (p = 0.040). This association was not significant for relapsed patients. In the subgroup of patients with newly diagnosed Ewing sarcoma classified as standard risk, we found higher risk of relapse or refractory disease associated with those samples that produced stable PDX models (p = 0.0357). Overall, our study shows that PDX engraftment predicts worse outcome in newly diagnosed pediatric sarcoma patients.

Hidrocefalia por hiperplasia de plexos coroideos en un paciente con mosaicismo de trisomía 9. Un verdadero reto diagnóstico y terapéutico / Hydrocephalus due to hyperplasia of the choroid plexuses in a patient with trisomy 9 mosaicism. A real diagnostic and therapeutic challenge

Introducción. La trisomía 9 es una cromosomopatía inusual en pacientes nacidos vivos, que frecuentemente se acompaña de anomalías funcionales y estructurales del sistema nervioso central. Entre otras muchas alteraciones, varios trabajos en la bibliografía anglosajona demuestran una asociación entre cromosomopatía 9 y patología de los plexos coroideos. Caso clínico. Varón de 4 meses de vida con mosaicismo de trisomía 9 asociado a hidrocefalia secundaria a hiperplasia de los plexos coroideos, que fue remitido por clínica de hipertensión intracraneal. El procedimiento derivativo de líquido cefalorraquídeo por el que optamos inicialmente provocó una ascitis masiva debida a la producción desmesurada de líquido cefalorraquídeo, y desembocó en una cascada de múltiples intervenciones quirúrgicas, entre las que se incluyeron procedimientos endoscópicos y derivativos. Conclusiones. Se trata de un ejemplo más de asociación entre patología de los plexos coroideos y cromosomopatía 9. Debido a su escasa incidencia, es difícil establecer el diagnóstico de hidrocefalia secundaria a hiperplasia de los plexos y, por tanto, el tratamiento más adecuado. En este tipo de hidrocefalia existe un doble mecanismo fisiopatológico, que implica un aumento de producción de líquido cefalorraquídeo y una disminución de su reabsorción. A pesar de tener en cuenta dicha consideración, el tratamiento de la hidrocefalia secundaria a hiperplasia de los plexos supone un verdadero reto que habitualmente pasa por múltiples procedimientos quirúrgicos, desde la plexectomía o coagulación de los plexos coroideos hasta la implantación de dispositivos de derivación de líquido cefalorraquídeo (AU)

Introduction. Trisomy 9 is an unusual chromosome abnormality in live-born patients, which is frequently accompanied by functional and structural anomalies of the central nervous system. Among many other alterations, several studies have been published in the English-speaking literature that show an association between chromosome 9 abnormality and pathologies affecting the choroid plexuses. Case report. We report the case of a 4-month-old male with trisomy 9 mosaicism associated to hydrocephalus secondary to choroid plexus hyperplasia, who was referred due to a clinical picture of intracranial hypertension. The cerebrospinal fluid (CSF) drainage procedure that was initially chosen caused massive ascites due to an excessive production of CSF, and led to a cascade of multiple surgical interventions, which included endoscopic and drainage procedures. Conclusions. This is another example of an association between choroid plexus pathologies and chromosome 9 abnormality. Due to its scarce incidence, diagnosis of hydrocephalus secondary to plexus hyperplasia is difficult, as is selecting its most suitable treatment. In this type of hydrocephalus there is a double pathophysiological mechanism, which involves an increase in CSF production and a decrease in its reabsorption. Despite taking these considerations into account, the treatment of hydrocephalus secondary to plexus hyperplasia is a real challenge that usually leads to multiple surgical interventions ranging from plexectomy or coagulation of the choroid plexuses to the implantation of CSF drainage devices (AU)

Tratamiento del pectus excavatum mediante toracoplastia percutánea videoasistida / Treatment of pectus excavatum with videoassisted percutaneous thoracoplasty

Fundamento. La deformación congénita más frecuentede la caja torácica es el pectus excavatum (PE): 95% de loscasos. PE es una malformación de los cartílagos costalesque comporta la respiración paradójica o invertida del pacientedesde la fase de la lactancia con hundimiento progresivodel esternón y deformación de toda la caja torácica.El tratamiento clásico del PE ha consistido entoracoplastia «a demanda» con resección subpericondralde todas las uniones costoesternales patológicas. La posibilidadde tratar esta afección mediante una técnica pocoinvasiva es una consideración que se debe evaluar.Objetivo. La finalidad de este trabajo es la presentaciónde nuestra experiencia en el tratamiento del PE mediantetoracoplastia percutánea videoasistida (TPV) segúnla técnica descrita por Nuss.Método. Desde el 14 de junio de 2001 a mayo de 2004hemos tratado 21 casos de PE grave mediante TPV. Todoslos casos correspondían a hombres de edades comprendidasentre 3 y 21 años (media edad: 10,4). Las exploracionescomplementarias requeridas son RX de tórax simple, pruebasde función respiratoria, ecocardiografía y TAC torácica conmedición de Indice de Haller (diámetro máximo LL / diámetromínimo del PE, considerando patológico un índice superior a3,2). El método quirúrgico se realiza bajo anestesia convencionale intubación orotraqueal. Con asistencia toracoscópicade 5 mm colocada en 7º espacio intercostal derecho seprocede a la reducción de la deformación y ferulización ortésicamediante una férula previamente configurada.Resultados. El tiempo medio ha sido de 65 minutos. Laspérdidas hemáticas son inapreciables (10-20 ml). Estanciamedia de 6.5 días. Como complicación se apreció un seroma en dos casos y granulomas en uno. La ortesis ha sido bientolerada en todos los casos, reintegrándose a su vida normala los 16 días de media. La férula ha sido ya retirada enseis pacientes por finalización del tratamiento. Todos loscasos se han reintegrado socialmente, y se ha conseguidouna adaptación rápida a la actividad física escolar. Seis pacientesque previamente presentaban cuadros bronconeumónicosde repetición no los han vuelto a sufrir. El resultadoestético es evidente desde la salida del quirófano, yaque únicamente se detectan tres pequeñas señales, quecon el tiempo se hacen imperceptibles. El beneficio económicose cifra en un 40% del procedimiento convencional.Conclusiones. Consideramos la TPV como un métodoatractivo del cual se pueden beneficiar todos los pacientesafectos de PE simétrico severo con independencia de suedad

Background. Pectus excavatum (PE) is the most commoncongenital malformation of the chest wall, accountingfor 95% of all cases. PE is a deformity of the cartilages ofthe chondrosternal joint that leads to inverted breathingand progressive chest deformity. Classic repair of PE is openthoracoplasty with subperichondral resection of the chondrosternaljoints. Alternative, less aggressive procedures,with minimally invasive techniques should be considered.Objective. The aim of this paper is to present our experiencein the treatment of PE with videoassisted percutaneousthoracoplasty (VPT), as previously described by Nuss.Patients and Methods. From June 2001 to May 2004,21 patients with severe PE were treated with VPT in our institution.All the patients were males, aged 3 to 21 years(mean 10.4 years). Chest XR, pulmonary function tests,echocardiography, and CT scan with measurement ofHaller index (LL diameter / AP diameter on the PE, andconsidering abnormal a ratio > 3.2) were the required diagnosticprocedures. Surgery was performed under generalanesthesia, with orotracheal intubation. The deformitywas corrected with the placement of previouslyconformed orthesis using videoassisted thoracoscopythrough the 7th intercostal space.Results. The mean duration of the intervention was 65minutes. Blood losses were minimal (10-20 ml), and themean length of hospitalization was 6.5 days (range 5 to 14days). Complications included seroma in 2 cases andwound granuloma in 1 case. The pectus bar was well toleratedin all patients, and normal activity was reached at amean of 16 days. The pectus bar was removed in 6 patientsonce the treatment was completed, and no recurrenceswere observed. Six patients that had history of recurrentbronchopulmonary infections prior to the correction are freeof symptoms. The good cosmetic outcome was apparent immediatelyafter surgery. Medical costs of this technique wereestimated to be 40% of the traditional techniques.Conclusions. The VPT is an effective minimally invasivesurgical technique that can be used in the treatment of allpatients with symmetric PE, regardless of age

Trefoil factor family peptide 3 prevents the development and promotes healing of ischemia-reperfusion injury in weanling rats.

BACKGROUND/PURPOSE: Although the pathogenesis of necrotizing enterocolitis (NEC) is not completely defined, ischemia appears to be one of the most important causative factors. Trefoil factor family peptide 3 (TFF3) is a peptide normally expressed in the small bowel and colon and is involved in the maintenance and repair of mucosal integrity. The authors hypothesized that monomeric (TFF3 Ser57) and dimeric (TFF3 Cys57) recombinant TFF3 may prevent the development and accelerate healing of intestinal ischemia-reperfusion injury in weanling rats. METHODS: Intestinal injury was induced in 18-day-old rats by occlusion of the superior mesenteric vessels for 60 minutes. To examine the protective effect, rats were given 3 microg/g of TFF3 Ser57 or TFF3 Cys57 by subcutaneous or enteral administration 30 minutes before the vascular occlusion. To examine the healing effect, rats were given 3 microg/g of TFF3 Ser57 or TFF3 Cys57 by subcutaneous or enteral administration 60 minutes after the beginning of reperfusion. Samples from small bowel and colon were collected for morphometric analysis after 3 hours of reperfusion. Mucosal damage was assessed by the Chiu score. RESULTS: Both forms of TFF3 reduced the amount of damage when administered before the ischemia. Administration of TFF3 Ser57 and TFF3 Cys57 after the beginning of reperfusion significantly increased the villous height and decreased the Chiu score in the small intestine and colon. CONCLUSIONS: TFF3 Ser57 monomer and TFF3 Cys57 dimer prevent the development and promote healing of ischemia-reperfusion injury in weanling rats. There are no differences between the routes of administration of TFF3.