Simone de Campos Vieira Abib

MYCN Gene Amplification: Identification of Cell Populations Containing Double Minutes and Homogeneously Staining Regions in Neuroblastoma Tumors

Neuroblastoma is the second most common solid tumor occurring in children. Amplification of the MYCN oncogene is associated with poor prognosis. To identify neuroblastoma tumors with MYCN amplification, we studied the number of copies of MYCN in interphase cells by fluorescence in situ hybridization in 20 neuroblastoma patients. MYCN amplification appeared in 7 tumor specimens. Interphase and metaphase studies showed a tumor cell population with both forms of amplification, double minutes and homogeneously staining regions, in two patients. These patients showed a smaller tumor cell subpopulation with the presence of more than one homogeneously staining region, suggesting that gene amplification was undergoing karyotype evolution.

Cavectomy for the Treatment of Wilms Tumor With Vascular Extension

PURPOSE Vascular extension to the vena cava occurs in 4% of Wilms tumor cases and can reach the right atrium in up to 1%. When this happens the thrombus is usually not adherent to the vessel wall, and there is blood flow around it. Preoperative chemotherapy can cause thrombus regression and even resolution. If the thrombus persists after chemotherapy, surgery will be a challenge. On the other hand, if the thrombus invades the vessel wall, its removal may not be feasible. In this situation cavectomy is a good surgical strategy because it provides complete resection. The prerequisite for cavectomy is the absence of blood flow in the vena cava on preoperative Doppler ultrasonography. We report 3 cases of Wilms tumor with vena caval invasion in which cavectomy was performed, and discuss the principles, indications and operative technique. MATERIALS AND METHODS A total of 171 patients with Wilms tumor were treated at our institution between 1984 and 2004. Of these patients 6 with intravascular extension of thrombus within the right atrium were treated with extracorporeal circulation, cardiac arrest and profound hypothermia, and 3 were treated with cavectomy. RESULTS There were no instances of surgical complications or postoperative renal failure in our patients who underwent cavectomy. All remain well and free of disease. CONCLUSIONS Cavectomy is a safe procedure for treating pediatric patients with Wilms tumor when there is extension and invasion of the vena cava wall without blood flow.

To Shunt or Not to Shunt? An Experimental Study Comparing Temporary Vascular Shunts and Venous Ligation as Damage Control Techniques for Vascular Trauma

BACKGROUND To evaluate vascular flow through temporary vascular shunts inserted into peripheral arteries and veins and the repercussion, on the arterial perfusion, of venous ligation and venous shunt insertion in an experimental model for damage control. METHODS Experimental study in pigs. Animals were distributed in 5 groups: group 1, right external iliac artery (EIA) shunting and right external iliac vein (EIV) ligation; group 2, right EIA shunting and right EIV shunting; group 3, right EIV ligation; group 4, right EIV shunting; group 5, no vascular shunting and no venous ligation. Flowmeters were used to measure vascular flow on right and left external iliac vessels, and blood samples were collected from the EIVs for biochemical analysis. A right anterior limb biopsy was performed before shock. Hemorrhagic shock was induced through the external right jugular vein, until the vascular flow through right iliac external artery shunt or right iliac external vein shunt (group 4) ceased or until the animals death. After the end of the experiments, biopsies of bilateral hind limb were obtained for histologic analysis. For statistical analysis, Microsoft Office Excel 2007 and BioEstat 5.0 (2007) were used. RESULTS In the absence of hemorrhagic shock, venous ligation (group 1) was associated with a 38.8% reduction (P < 0.05) and venous shunting with a 28.4% reduction on the vascular flow through the arterial shunt. When associated with hemorrhagic shock, the mean vascular flow on the right EIA was 13 mL/min and on the left EIA was 41.2 mL/min; on group 2, the right EIA flow was 8.5 mL/min and the left EIA flow was 8.1 mL/min. When associated with hemorrhagic shock, the pO2 was 25.8 mm Hg on right EIV and 33.8 mm Hg on the left EIV for group 1 (P < 0.05), whereas for group 2, the pO2 was 22.6 mm Hg on right EIV and 22.8 mm Hg on the left EIV. On group 1, serum potassium was 3.84 mEq/L on the right EIV and 3.96 mEq/L on the left EIV, whereas on group 2, it was 7.1 mEq/L on the right EIV and 5.88 mEq/L on the left EIV (P < 0.05). CONCLUSIONS In the developed experimental model, venous shunting, when compared with venous ligation, offered less resistance to vascular flow through the arterial shunt and allowed a more efficient limb venous drainage than simple vein ligature.

Long‐term complications in totally implantable venous access devices: Randomized study comparing subclavian and internal jugular vein puncture

This prospective randomized study evaluated complications related to long‐term totally implantable catheters in oncologic children and adolescents by comparing venopunction performed either in the jugular or subclavian vein.

Investigation of PAX3/7-FKHR fusion genes and IGF2 gene expression in rhabdomyosarcoma tumors

The purpose of our study was to investigate the prevalence of the PAX3/7-FKHR fusion genes and quantify the IGF2 gene expression in rhabdomyosarcoma (RMS) samples. Soft tissue sarcomas account 5% of childhood cancers and 50% of them are RMS. Morphological evaluation of pediatric RMS has defined two histological subtypes, embryonal (ERMS) and alveolar (ARMS). Chromosomal analyses have demonstrated two translocations associated with ARMS, resulting in the PAX3/7-FKHR rearrangements. Reverse transcriptase-polymerase chain reaction (RT-PCR) is extremely useful in the diagnosis of ARMS positive for these rearrangements. Additionally, several studies have shown a significant involvement of IGF pathway in the pathogenesis of RMS. The presence of PAX3/7-FKHR gene fusions was studied in 25 RMS samples from patients attending the IOP-GRAACC/UNIFESP and three RMS cell lines by RT-PCR. IGF2 gene expression was quantified by qPCR and related with clinic pathological parameters. Of the 25 samples, nine (36%) were ARMS and 16 (64%) were ERMS. PAX3/7-FKHR gene fusions expression was detected in 56% of ARMS tumor samples. IGF2 overexpression was observed in 80% of samples and could indicate an important role of this pathway in RMS biology.

An evaluation of the professional, social and demographic profile and quality of life of physicians working at the Prehospital Emergency Medical System (SAMU) in Brazil

OBJECTIVE: To describe the profile of physicians working at the Prehospital Emergency Medical System (SAMU) in Brazil and to evaluate their quality of life. METHODS: Both a semi-structured questionnaire with 57 questions and the SF-36 questionnaire were sent to research departments within SAMU in the Brazilian state capitals, the Federal District and inland towns in Brazil. RESULTS: Of a total of 902 physicians, including 644 (71.4%) males, 533 (59.1%) were between 30 and 45 years of age and 562 (62.4%) worked in a state capital. Regarding education level, 45.1% had graduated less than five years before and only 43% were specialists recognized by the Brazilian Medical Association. Regarding training, 95% did not report any specific training for their work at SAMU. The main weaknesses identified were psychiatric care and surgical emergencies in 57.2 and 42.9% of cases, respectively; traumatic pediatric emergencies, 48.9%; and medical emergencies, 42.9%. As for procedure-related skills, the physicians reported difficulties in pediatric advanced support (62.4%), airway surgical access (45.6%), pericardiocentesis (64.4%) and thoracentesis (29.9%). Difficulties in using an artificial ventilator (43.3%) and in transcutaneous pacing (42.2%) were also reported. Higher percentages of young physicians, aged 25-30 years (26.7 vs 19.0%; p<0.01), worked exclusively in prehospital care (18.0 vs 7.7%; p<0.001), with workloads >48 h per week (12.8 vs 8.6%; p<0.001), and were non-specialists with the shortest length of service (<1 year) at SAMU (30.1 vs 18.2%; p<0.001) who were hired without having to pass public service exams* (i.e., for a temporary job) (61.8 vs 46.2%; p<0.001). Regarding quality of life, the pain domain yielded the worst result among physicians at SAMU. CONCLUSIONS: The doctors in this sample were young and within a few years of graduation, and they had no specific training in prehospital emergencies. Deficiencies were mostly found in pediatrics and psychiatry, with specific deficiencies in the handling of essential equipment and in the skills necessary to adequately attend to prehospital emergencies. A disrespectful labor scenario was also found; the evaluation of quality of life showed a notable presence of pain on the SF-36 among physicians at SAMU and especially among doctors who had worked for a longer length of time at SAMU.

Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model.

Entrapped victims in motor vehicle collisions: characteristics and prehospital care in the city of São Paulo, Brazil

OBJECTIVE: To examine the severity of trauma in entrapped victims and to identify risk factors for mortality and morbidity. INTRODUCTION: Triage and rapid assessment of trauma severity is essential to provide the needed resources during prehospital and hospital phases and for outcome prediction. It is expected that entrapped victims will have greater severity of trauma and mortality than non‐entrapped subjects. METHODS: A transverse, case–control, retrospective study of 1203 victims of motor vehicle collisions treated during 1 year by the prehospital service in São Paulo, Brazil was carried out. All patients were drivers, comprising 401 entrapped victims (33.3%) and 802 non‐entrapped consecutive controls (66.7%). Sex, age, mortality rates, Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), corporal segments, timing of the prehospital care and resource use were compared between the groups. The results were analysed by χ2, Zres, analysis of variance and Bonferroni tests. RESULTS: Entrapped victims were predominantly men (84.8%), aged 32±13.1 years, with immediate mortality of 10.2% and overall mortality of 11.7%. They had a probability of death at the scene 8.2 times greater than that of non‐entrapped victims. The main cause of death was hemorrhage for entrapped victims (45.2%) and trauma for non‐entrapped victims. Of the entrapped victims who survived, 18.7% had a severe GCS (OR = 10.62), 12% a severe RTS (OR = 9.78) and 23.7% were in shock (OR = 3.38). Entrapped victims were more commonly transported to advanced life support units and to tertiary hospitals. CONCLUSION: Entrapped victims had greater trauma severity, more blood loss and a greater mortality than respective, non‐entrapped controls.

Investigation of IGF2, Hedgehog and fusion gene expression profiles in pediatric sarcomas

UNLABELLED The childhood sarcomas are malignant tumors with high mortality rates. They are divided into two genetic categories: a category without distinct pattern karyotypic changes and the other category showing unique translocations that originate gene rearrangements. This category includes rhabdomyosarcoma (RMS), Ewings sarcoma (ES) and synovial sarcoma (SS). Diverse studies have related development genes, such as; IGF2, IHH, PTCH1 and GLI1 and sarcomatogenesis. OBJECTIVE To characterize the RMS, ES and SS rearrangements, we quantify the expression of IGF2 IHH, PTCH1 and GLI1 genes and correlate molecular data with clinical parameters of patients. DESIGN We analyzed 29 RMS, 10 SS and 60 ES tumor samples by RT-PCR (polymerase chain reaction-reverse transcription) and qPCR (quantitative PCR). RESULTS Among the samples of ARMS, 50% had rearrangements of PAX3/7-FOXO1, 60% of ES samples were EWS-FLI1 positive and 90% of SS samples were positive for SS18-SSX1/2. In relation to the control reference samples (QPCR Human Reference Total RNA-Stratagene, Human Skeletal Muscle Total RNA-Ambion, Universal RNA Human Normal Tissues-Ambion), RMS samples showed a high IGF2 gene expression (p<0.0001). Moreover, ES samples showed a low IGF2 gene expression (p<0.0001) and high IHH (p<0.0001), PTCH1 (p=0.0173) and GLI1 (p=0.0113) gene expressions. CONCLUSIONS The molecular characterization of IGF and Hedgehog pathway in these pediatric sarcomas may collaborate to enable a better understanding of the biological behavior of these neoplasms.

Endovascular Treatment of Giant Splenic Artery Aneurysm

Introduction. Visceral artery aneurysms are uncommon. Among them, splenic artery is the most common (46–60%). Most splenic artery aneurysms are asymptomatic and diagnosed incidentally, but its rupture, potentially fatal, occurs in up to 8% of cases. Presentation of Case. A female patient, 64 years old, diagnosed with a giant aneurysm of the splenic artery (approximately 6.5 cm in diameter) was successfully submitted to endovascular treatment by stent graft implantation. Discussion. Symptomatic aneurysms and those larger than 2 cm represent some of the main indications for intervention. The treatment may be by laparotomy, laparoscopy, or endovascular techniques. Among the various endovascular methods discussed in this paper, there is stent graft implantation, a method still few reported in the literature. Conclusion. Although some authors still consider the endovascular approach as an exception to the treatment of SAA, in major specialized centers these techniques have been consolidated as the preferred choice, reserving the surgical approach in cases where this cannot be used. For being a less aggressive approach, it offers an opportunity of treatment to patients considered “high risk” for surgical treatment by laparotomy/laparoscopy.