Risks and benefits of ending of mass screening for neuroblastoma at 6 months of age in Japan

Purpose

The mass screening (MS) for neuroblastoma (NB) at 6 months of age in Japan was discontinued in 2004. This study assessed the risks and benefits of MS based on an analysis of NB detected before or after discontinuation of MS in Japan.

Methods

The clinical features and Brodeur's genetic type based on MYCN, DNA ploidy, and other genetic aberrations were assessed in 113 NB patients (20 cases after and 93 cases [55 MS cases] before the discontinuation of MS) older than 6 months treated at one institution since 1985.

Results

The 20 patients with NBs detected after MS was discontinued ranged in age from 7 to 67 months, 12 patients were stage 4, and 11 patients would have been detected at 6 months of age if they had undergone MS. The Brodeur's genetic type of these 20 patients showed that 30% (6/20) were type 1 (low risk), 55% (11/20) were type 2A (intermediate risk), and 15% (3/20) were type 2B (high risk). Of 93 patients with NB detected before MS was discontinued, 60% (56/93) were type 1, 18% (17/93) were type 2A, and 22% (20/93) were type 2B. Among the type 2A patients, 82% (9/11) of the patients detected after MS was discontinued showed stage 4, whereas only 50% (9/18) of those diagnosed before MS was discontinued were stage 4. The genetic analysis using single nucleotide polymorphism (SNP) array for type 2A showed that the pattern of genetic aberration was equivalent in those detected either before or after MS was discontinued.

Conclusions

There was a decrease of type 1 and an increase of type 2A NB in patients after MS was discontinued in Japan. These results suggest that most of the type 1 detected by MS has regressed, and most of the type 2A detected by MS has appeared sporadically as advanced NB in patients older than 1 year.     

Intense FDG uptake in the ovary with painless torsion

We report a case demonstrating intense FDG uptake in the ovary, which was diagnosed to be a hemorrhage and congestion due to painless torsion. An asymptomatic retropelvic mass was detected in a 51-year-old female by echography. FDG-PET demonstrated intense uptake in the mass, thus suggesting an ovarian tumor. A resection of the tumor was performed, and histopathological examination revealed hemorrhage and congestion in the ovary due to ovarian torsion. An ovarian hemorrhage due to painless torsion should be considered in the differential diagnosis of intrapelvic masses demonstrating high FDG uptake, even in asymptomatic patients.     

Platelets Promote Liver Regeneration in Early Period after Hepatectomy in Mice

Background Platelets contain several growth factors, including platelet-derived growth factor and hepatocyte growth factor. Materials and methods We examined the effects of platelet increment on liver regeneration after 70% hepatectomy. Hepatectomies were carried out in male BALB/c mice, and subsequently divided into three groups: (i) untreated mice, (ii) thrombocytotic mice induced with thrombopoietin, and (iii) thrombocytopenic mice induced with anti-platelet antibody. Growth kinetics in the liver were analyzed as a function of the liver/body weight ratio, the mitotic index, the proliferating cell nuclear antigen labeling index and Ki-67 labeling index. Activation of signal transduction pathways relating to cell proliferation were examined, including the STAT3, Akt, and ERK1/2 pathways. Platelet accumulation in the residual liver was quantified by immunohistochemistry and transmission electron microscopy. Results In thrombocytotic and thrombocytopenic mice, liver/body weight ratios and Ki-67 labeling indices were significantly increased and significantly decreased, respectively, compared with untreated mice 48 hours post-hepatectomy. The Akt pathway was strongly activated, and platelet accumulation was significantly increased in thrombocytotic group 5 minutes post-hepatectomy compared with normal and thrombocytopenic groups. After hepatectomy platelets accumulated in the sinusoids of liver and promoted hepatocyte proliferation in early period after hepatectomy. Conclusion By increasing or decreasing the platelet, marked changes in liver regeneration can occur, due to differences in cellular signaling and mitosis.     

Clinical evaluation of biapenem for febrile neutropenia in patients with hematological disorders

We examined the clinical evaluation of biapenem (BIPM) for febrile neutropenia in patients with hematological disorders. BIPM was administrated by drip infusion when fever developed over 37.5 degrees C with a neutrophil counts lower than 1000/microl. The underlying diseases were acute myelogenous leukemia in 16 cases, acute lymphocytic leukemia in 1, malignant lymphoma in 14, myelodysplastic syndrome in 1, aplastic anemia in 1. Microbiologically documented infections were found in 3 cases (9.1%) before treatment. Clinical effect was excellent in 9 cases, good in 11, fair in 6, poor in 7. Factors associated with efficacy rate were concomitant use of granulocytecolony stimulating factor, duration of neutropenia and neutrophil counts at day 3 of day after start of the therapy. No serious adverse events were observed in all cases, although one case developed exanthema. In conclusion, these results confirmed the efficacy and safety of BIPM for febrile neutropenia in patients with hematological disorders.     

Effect of inhaled KP-496, a novel dual antagonist of the cysteinyl leukotriene and thromboxane A2 receptors,on a bleomycin-induced pulmonary fibrosis model in mice

Cysteinyl-leukotrienes (cysLTs) and thromboxane A₂ (TXA₂) are important mediators in inflammatory lung diseases such as bronchial asthma and idiopathic pulmonary fibrosis (IPF). We examined the effects of inhaled KP-496, a novel dual antagonist of the cysLTs and TXA₂ receptors, on bleomycin-induced IPF in mice. Mice were intravenously injected bleomycin on day 0, and 0.5% of KP-496 was inhaled twice a day (30 min/time) for the entire experimental period. The effects of KP-496 were evaluated by the number of infiltrated cells in bronchoalveolar lavage fluid (BALF), hydroxyl-l-proline content in the lung, and histopathology. Analyses of BALF on days 7 and 21 revealed that inhaled KP-496 significantly decreased total cell numbers, macrophages, neutrophils, and eosinophils on both days. KP-496 significantly decreased hydroxyl-l-proline content in the lung on day 21. Histopathological analyses of lungs on day 21 demonstrated that KP-496 significantly suppressed inflammatory and fibrotic changes. Our results suggested that the suppression of cysLTs and TXA₂ pathways by KP-496 could control airway inflammation and pulmonary fibrosis, and that KP-496 could be a new therapeutic agent for lung diseases with inflammation and fibrogenesis such as IPF and chronic obstructive pulmonary disease.     

Genotyping and phylogenetic analysis of the major genes in respiratory syncytial virus isolated from infants with bronchiolitis

We performed the genotyping and phylogenetic analysis of respiratory syncytial virus (RSV) isolated from 17 infants with bronchiolitis in Kanagawa Prefecture, Japan in 2005 and 2006. The major genes in these samples (attachment [G] glycoprotein gene, fusion [F] protein gene, and nucleoprotein [N] gene) were sequenced and analyzed genetically. Phylogenetic analysis of these genes revealed that 7 and 10 strains could be classified into subgroups A and B, respectively. Phylogenetic analysis of the G gene revealed that the subgroup A and B strains were unique genotypes GA2 and BA, respectively. Moreover, the amino acid sequences for these genotypes suggested a relatively high frequency of amino acid substitutions in the G and F proteins in these strains, whereas the N protein was highly homologous. These results suggest that RSV genotypes GA2 and BA may be associated with bronchiolitis in the cases studied here.     

Insufficiency fracture at the distal diaphysis of the radius after synovectomy combined with the Sauvé-Kapandji procedure in a patient with rheumatoid arthritis

We report here a rare case of insufficiency fracture at the distal diaphysis of the radius in a patient with rheumatoid arthritis (RA) after synovectomy combined with the Sauvé-Kapandji procedure. A 71-year-old woman who had been diagnosed with RA had been consecutively treated with several disease-modifying antirheumatic drugs. She had undergone synovectomy of the right wrist combined with the Sauvé-Kapandji procedure, due to a tendon rupture, 2 years before the current presentation (first visit). Although she had not experienced any recent trauma, the wrist pain had increased after she had lifted up the bedding at the funeral of her friend about 1 month prior to her first visit. Radiographs of her right wrist taken at the second visit showed a fracture at the distal diaphysis of the radius at the level of the excision osteotomy of the distal ulna; however, no displacement of the distal fragment was observed. We immobilized her forearm in a long-arm cast. However, after 3 weeks of cast immobilization, a displacement of the distal fragment was observed. A manual reduction of the displacement was performed and the arm was again immobilized in a long-arm cast. However, 1 week later, a displaced distal fragment was again observed. Subsequently, she received an open reduction and internal fixation using a volar locking plate and screws with an autologous iliac crest bone graft. Bone union was completed by 8 months following the operation.