Monica Cypriano

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.

Evaluation of ticarcillin/clavulanic acid versus ceftriaxone plus amikacin for fever and neutropenia in pediatric patients with leukemia and lymphoma

BACKGROUND The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia. Intravenous monotherapy, with broad spectrum antibiotics, of patients with a high risk of complications is a possible alternative. METHODS We conducted a prospective open-label, randomized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy. Patients received either monotherapy with ticarcillin/clavulanic acid (T) or ceftriaxone plus amikacin (C+A). RESULTS Seventy patients who presented 136 episodes were evaluated, 68 in each arm of the study. The mean neutrophil counts at admission were 217cells/mm(3) (T) and 201cells/mm(3) (C+A). The mean duration of neutropenia was 8.7 days (T) and 7.6 days (C+A). Treatment was successful without the need for modifications in 71% of the episodes in the T group and 81% in the C+A group (p=0.23). Treatment was considered to have failed because of death in two episodes (3%) in the T group and three episodes (4%) in the C+A group, and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group. Overall success was 96% (T) and 93% (C+A). Adverse events that occurred in group T were not related to the drugs used in this study. CONCLUSION In pediatric and adolescent patients with leukemia or lymphoma, who presented with fever and neutropenia, during chemotherapy, ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin. It should be considered an appropriate option for this group of patients at high risk for infections.

Fifteen Years' Experience of the Brazilian Osteosarcoma Treatment Group (BOTG): A Contribution from an Emerging Country.

PURPOSE Little information is available regarding the tumor features, prognostic factors, and treatment results in children and adolescents and young adults (AYAs) with osteosarcoma diagnosed in developing countries. We reviewed the results of three observational cohorts of osteosarcoma patients treated in an emerging country. METHODS A total of 604 patients below the age of 30 years with high-grade osteosarcoma were prospectively enrolled in the Brazilian Osteosarcoma Treatment Group (BOTG) studies III, IV, and V. Gender, age, time from onset of symptoms to diagnosis, primary tumor site, presence or absence of metastases at diagnosis, tumor size, type of surgery (limb-sparing or amputation), treatment protocol, and histological response were correlated with survival. RESULTS The estimated 5-year overall survival and event-free survival (EFS) rates for the 553 eligible patients were 49% and 39% respectively; of the 390 non-metastatic patients included in the total, overall- and event-free survival were 59% and 48% respectively. Metastases at diagnosis, primary tumor site, type of surgery, and histological response were significant predictors of overall survival and EFS in univariate and multivariate analysis, whereas tumor size and treatment protocol lost prognostic significance in multivariate analysis. CONCLUSION We report on the outcome of three consecutive studies for the treatment of osteosarcoma carried out in Brazil over 15 years. Although the survival rates presented are below those reported in current literature, it represents the result of a favorable experience gathered from the national collaborative work.

DNA methylation landscape of hepatoblastomas reveals arrest at early stages of liver differentiation and cancer-related alterations

Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation. The analysis revealed 1,359 differentially methylated CpG sites (DMSs) between hepatoblastomas and control livers, which are associated with 765 genes. Hypomethylation was detected in hepatoblastomas for ~58% of the DMSs with enrichment at intergenic sites, and most of the hypermethylated CpGs were located in CpG islands. Functional analyses revealed enrichment in signaling pathways involved in metabolism, negative regulation of cell differentiation, liver development, cancer, and Wnt signaling pathway. Strikingly, an important overlap was observed between the 1,359 DMSs and the CpG sites reported to exhibit methylation changes through liver development (p<0.0001), with similar patterns of methylation in both hepatoblastomas and fetal livers compared to adult livers. Overall, our results suggest an arrest at early stages of liver cell differentiation, in line with the hypothesis that hepatoblastoma ontogeny involves the disruption of liver development. This genome-wide methylation dysfunction, taken together with a relatively small number of driver genetic mutations reported for both adult and pediatric liver cancers, shed light on the relevance of epigenetic mechanisms for hepatic tumorigenesis.Hepatoblastomas are uncommon embryonal liver tumors accounting for approximately 80% of childhood hepatic cancer. We hypothesized that epigenetic changes, including DNA methylation, could be relevant to hepatoblastoma onset. The methylomes of eight matched hepatoblastomas and non-tumoral liver tissues were characterized, and data were validated in an independent group (11 hepatoblastomas). In comparison to differentiated livers, hepatoblastomas exhibited a widespread and non-stochastic pattern of global low-level hypomethylation. The analysis revealed 1,359 differentially methylated CpG sites (DMSs) between hepatoblastomas and control livers, which are associated with 765 genes. Hypomethylation was detected in hepatoblastomas for ~58% of the DMSs with enrichment at intergenic sites, and most of the hypermethylated CpGs were located in CpG islands. Functional analyses revealed enrichment in signaling pathways involved in metabolism, negative regulation of cell differentiation, liver development, cancer, and Wnt signaling pathway. Strikingly, an important overlap was observed between the 1,359 DMSs and the CpG sites reported to exhibit methylation changes through liver development (p<0.0001), with similar patterns of methylation in both hepatoblastomas and fetal livers compared to adult livers. Overall, our results suggest an arrest at early stages of liver cell differentiation, in line with the hypothesis that hepatoblastoma ontogeny involves the disruption of liver development. This genome-wide methylation dysfunction, taken together with a relatively small number of driver genetic mutations reported for both adult and pediatric liver cancers, shed light on the relevance of epigenetic mechanisms for hepatic tumorigenesis.