Growth hormone deficiency after localized ganglioneuroblastoma: A case report

Growth hormone deficiency (GHD) related to standard dose chemotherapy has rarely been described. We report on a case of localized ganglioneuroblastoma treated by carboplatin/etoposide for 2 courses and surgery, which developed a serious GHD after 56 months. At present, the child is growing on by GH replacement therapy. We discuss about the hypothesis that GHD may be related to chemotherapy and we report a review of previous published cases

Late Relapse of Botryoid Embryonal Rhabdomyosarcoma of the Vagina in Prepubertal Age

[No abstract available

Congenital Stage 1 Neuroblastoma Evolved Into Stage 4s

A newborn with a prenatally detected adrenal mass underwent complete resection of it Stage 1 favorable histology neuroblastoma (NB) without MYC-N amplification. Two months later. the infant presented with a local recurrence and multiple hepatic metastases. Close follow-up without therapy was adopted for stage 4s NB. Enlarging tumor lesions were seen until the child was S months old. followed by later decrease in size. At 36 months of follow-up. the child is alive and disease-free. We describe this case of NB and its abnormally short evolution from stage 1 to stage 4s. despite initial surgery. Its Spontaneous regression May help us understand the natural history of congenital NB

Barrett Esophagus in Long-term Survivors of Childhood Solid Tumors

We report on 2 cases of long-term survivors of childhood solid tumors, who developed Barrett esophagus (BE) after treatment for neuroblastoma and Hodgkin lymphoma, respectively. Case 1: A stage 3 neuroblastoma was treated with surgery, carboplatin/etoposide chemotherapy, and supradiaphragmatic radiotherapy (30 Gy). Twelve years later, based on endoscopic and histologic findings, BE was diagnosed on the middle segment. Case 2: A stage IIIB Hodgkin lymphoma received mechloretamine, oncovin, procarbazine, prednisone/adriamycin, bleomycin, vinblastine, dacarbazine chemotherapy and supra/subdiaphragmatic radiotherapy (25 Gy). Nineteen years later, BE was diagnosed associated with an esophageal stricture. In long-term survivors of childhood tumors who had received chest/neck radiotherapy and chemotherapy, the risk of BE may be increased, therefore the diagnosis should be considered in the presence of gastroesophageal symptoms

Venous thrombosis in children with solid tumors

Background: The prevalence of venous thrombosis (VT) in children with solid tumor and the role of different risk factors are not defined yet. Aim: A cross-sectional observational study was conducted to evaluate the prevalence of both symptomatic and asymptomatic catheter-associated thrombosis events in children affected with different solid tumors. Methods: Patients with a solid tumor, admitted as day-care, were consecutively enrolled over a period of 10 months. All of them had a central venous line. Physical examination, D-dimer serum tests, and eco-color-Doppler ultrasonography were performed once at any time before catheter removal. Results: Forty-two patients (14 females and 28 males)-mean age 115 months-were evaluated. Five of the 42 patients (12%) had VT. In 4 of these, VT was catheter-related: 3 asymptomatic and I symptomatic. In the last patient, VT was clinically symptomatic and not catheter related. Patients with longer duration of catheter insertion presented with a higher rate of VT (P = 0.05). Moreover, patients affected with neuroblastoma showed a higher rate of VT than the others with different solid tumors (P < 0.05). Conclusions: VT was visualized by echo-color-Doppler ultrasonography in 12% of the patients; it was asymptomatic in 7%. In our small series, VT was related to neuroblastoma disease and a longer duration of catheter insertion. Prospective and multicentric studies are required to select risk factors for VT in children with solid tumors

Venous thrombosis and procoagulant factors in high-risk neuroblastoma

Aim: The mechanism of increased thrombin production has been investigated in children with high-risk neuroblastoma (NB), to detect any possible association between catheter- related venous thrombosis (VT) and prothrombotic factors. Methods: Consecutive children with high-risk NB were studied by color-doppler ultrasonography of the upper vein system and thrombophilia factors assessment. Plasma levels of Tissue Factor (TF), Vascular Endothelial Growth Factor (VEGF), Prothrombin Activation Fragment 1+2, and Thrombin-Antithrombin Complex were evaluated. Moreover, inherited thrombophilia factors (homocystein, antithrombin, protein C, protein S, factor V Leiden, activated protein C resistence, mutation H1299R and G1691A of factor V, mutation G20210A of prothrombin, mutation T677 and A1298C of methylenetetrahydrofolate reductase, and allele 4G of plasminogen activator inhibitor-1) were tested to exclude congenital disorders. Results: Six patients with mean age: 48.8 months - were studied. Five patients were affected by stage 4 NB and another one by stage 3 NB with Myc-N amplification. All children had a central venous line (mean duration: 8.5 mos). Four patients (67%) had asymptomatic catheter-related VT visualized by color-doppler ultrasonography. No patient had major inherited thrombophilia factors. The levels of plasma TF and plasma VEGF were found elevated in all patients. Mean value of TF (nv 20.3±6.6) was 82 pg/mL with a range of 39 to 131 pg/mL. Mean value of VEGF (nv 24.3 pg/mL) was 78.5 pg/mL with a range of 31 to 142 pg/mL. Conclusion: The increased risk of catheter-related VT detected in our small series of high-risk NB patients, was associated with elevated levels of circulating TF and VEGF. Further studies are needed to evaluate if elevated levels of TF/VEGF are involved both in the hypercoagulable state and in advanced childhood cancer

Zebrafish as a Model of Cardiac Pathology and Toxicity: Spotlight on Uremic Toxins

: Chronic kidney disease (CKD) is an increasing health care problem. About 10% of the general population is affected by CKD, representing the sixth cause of death in the world. Cardiovascular events are the main mortality cause in CKD, with a cardiovascular risk 10 times higher in these patients than the rate observed in healthy subjects. The gradual decline of the kidney leads to the accumulation of uremic solutes with a negative effect on every organ, especially on the cardiovascular system. Mammalian models, sharing structural and functional similarities with humans, have been widely used to study cardiovascular disease mechanisms and test new therapies, but many of them are rather expensive and difficult to manipulate. Over the last few decades, zebrafish has become a powerful non-mammalian model to study alterations associated with human disease. The high conservation of gene function, low cost, small size, rapid growth, and easiness of genetic manipulation are just some of the features of this experimental model. More specifically, embryonic cardiac development and physiological responses to exposure to numerous toxin substances are similar to those observed in mammals, making zebrafish an ideal model to study cardiac development, toxicity, and cardiovascular disease

Uremic Toxin Lanthionine Induces Endothelial Cell Mineralization In Vitro

: Vascular calcification (VC) is a pathological event caused by the unusual deposition of minerals in the vascular system, representing the leading cause of cardiovascular mortality in chronic kidney disease (CKD). In CKD, the deregulation of calcium and phosphate metabolism, along with the effect of several uremic toxins, act as key processes conveying altered mineralization. In this work, we tested the ability of lanthionine, a novel uremic toxin, to promote calcification in human endothelial cell cultures (Ea.hy926). We evaluated the effects of lanthionine, at a concentration similar to that actually detected in CKD patients, alone and under pro-calcifying culture conditions using calcium and phosphate. In pro-calcific culture conditions, lanthionine increased both the intracellular and extracellular calcium content and induced the expression of Bone Morphogenetic Protein 2 (BMP2) and RUNX Family Transcription Factor 2 (RUNX2). Lanthionine treatment, in pro-calcifying conditions, raised levels of tissue-nonspecific alkaline phosphatase (ALPL), whose expression also overlapped with Dickkopf WNT Signaling Pathway Inhibitor 1 (DKK1) gene expression, suggesting a possible role of the latter gene in the activation of ALPL. In addition, treatment with lanthionine alone or in combination with calcium and phosphate reduced Inorganic Pyrophosphate Transport Regulator (ANKH) gene expression, a protective factor toward the mineralizing process. Moreover, lanthionine in a pro-calcifying condition induced the activation of ERK1/2, which is not associated with an increase in DKK1 protein levels. Our data underscored a link between mineral disease and the alterations of sulfur amino acid metabolisms at a cell and molecular level. These results set the basis for the understanding of the link between uremic toxins and mineral-bone disorder during CKD progression

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines

Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of 2 and ≥45 mL/min/1.73 m2. Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR 2 with respect to those with GFR ≥ 45 mL/min/1.73 m2. IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance