Effects of the Cessation of Mass Screening for Neuroblastoma at 6 Months of Age: A Population-Based Study in Osaka, Japan.

BACKGROUND: In 2004, the Japanese government halted the 6-month mass screening program for neuroblastoma. We investigated whether its cessation had led to an increase not only in mortality due to this disease but also in the incidence of advanced-stage disease among older children. METHODS: Study subjects were neuroblastoma patients retrieved from the population-based Osaka Cancer Registry. Trends of incidence and mortality from neuroblastoma were analyzed by calendar year and birth cohort. Prognostic factors, including stage and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) oncogene status, were compared before and after the cessation of mass screening. RESULTS: Age-standardized incidence rates in 2005-2009 (the cessation period of mass screening; 11.1 per million) were similar to those in 1975-1979 (the pre-screening period; 8.6 per million). Age-standardized mortality rates tended to decrease from 1975-1979 (4.0 per million) to 2005-2009 (2.7 per million) in parallel with the improvement in survival. Analysis by birth cohort indicated that the mortality rates in 2004-2005 (after cessation) for children 0-4 years of age were lower than those in 1975-1979 (O:E ratio 0.25; 95% confidence interval, 0.03-0.90). For children 1-9 years of age, there was a not significant difference in the distribution of stage, MYCN oncogene status, and DNA ploidy between 1991-2003 (the mass screening period) and 2004-2008 (after cessation). CONCLUSIONS: The cessation of mass screening for neuroblastoma does not appear to have increased mortality due to this disease or incidence of advanced-stage disease among older children.

Successful emergency combined therapy with partial splenic arterial embolization and endoscopic injection therapy against a bleeding duodenal varix in a child.

There is no consensus guidelines for treating duodenal variceal bleeding, which is a rare and life-threatening complication of portal hypertension. Here we report an exceedingly unusual case in a 9-year-old boy who had developed left-sided portal hypertension after surgical treatment for pancreatoblastoma followed by a duodenal variceal bleeding with massive melena, severe anemia (hemoglobin 4.5 g/dL) and hypovolemic shock. Emergency partial splenic arterial embolization (PSE) provided a reduction of variceal bleeding and improved blood pressure. Endoscopic injection sclerotherapy (EIS) was subsequently performed and stopped the duodenal variceal bleeding without the complication of portal vein thrombosis caused by injected sclerosant under hepatopetal flow. Our case demonstrates that emergency combined therapy with PSE and EIS can be considered as the therapeutic option for the management of left-sided portal hypertension-induced ectopic variceal bleedings in order to avoid the complication of portal embolization by EIS and provide effective hematostasis.

Inferior outcomes of stage III T lymphoblastic lymphoma relative to stage IV lymphoma and T-acute lymphoblastic leukemia: long-term comparison of outcomes in the JACLS NHL T-98 and ALL T-97 protocols.

T cell lymphoblastic lymphoma (T-LBL) accounts for 30 % of all childhood non-Hodgkin's lymphomas (NHL) in Japan. Twenty-nine patients with T-LBL in stages III and IV were eligible for and enrolled in the JACLS NHL-T98 trial (1998-2002), and 72 patients with T-ALL were enrolled in the JACLS ALL-T97 trial (1997-2001). The 10-year overall survival (OS) (61.1 ± 11.5 %) and the 10-year event-free survival (EFS) (44.4 ± 11.7 %) of stage III LBL were lower than those of other diseases, and the OS and EFS were nearly the same when comparing stage IV LBL and ALL (OS: stage IV LBL, 80.0 ± 12.7 % vs. ALL, 80.2 ± 4.9 %; EFS: stage IV, LBL 70.0 ± 14.5 % vs. ALL, 70.7 ± 5.5 %). Outcomes were worse for stage III LBL than for stage IV LBL or T-ALL. Given that the treatment results of T-ALL and LBL stage IV did not differ when compared with previous reports, LBL stage III in Japanese children may differ from LBL stage III in children in other countries.

Diagnosis of osteosarcoma in a patient previously treated for Ewing sarcoma.

Primary malignant bone tumors, whether Ewing sarcoma or osteosarcoma, are a rare type of tumor. The sequential occurrence of two bone sarcomas, Ewing sarcoma and high-grade osteosarcoma, in the same patient at two different locations is an exceptionally rare phenomenon. We present the case of a 13-year-old girl who presented with a high-grade osteoblastic osteosarcoma of the distal femur, 7 years after treatment for Ewing sarcoma of the left pelvis. She did not receive radiation therapy. Following the recent developing multidisciplinary therapy, long-term follow-up for monitoring latent treatment-related adverse effects may be necessary for survivors of primary malignant bone tumors.

Microscopic polyangiitis in a girl with severe anemia and no respiratory symptoms.

ANCA-positive microscopic polyangiitis is a rare in children. We reported an 11-year-old girl without respiratory symptoms with sever anemia which shows signs of hemolytic anemia in test data. Chest X-ray and computed tomography scans suggested alveolar hemorrhage. The patent developed night hypoxia and moderate proteinuria. Serum MPO-antibody was highly positive and renal biopsy demonstrated segmental necrosis or crescent formation. A diagnosis of microscopic polyangiitis was made. She responded to pulsed methylprednisolon and pulsed Endoxan therapy. Microscopic polyangitiis should be considered early in the differential diagnosis of patients presenting with anemia of an unknown origin.

Clinical features and outcome of X-linked lymphoproliferative syndrome type 1 (SAP deficiency) in Japan identified by the combination of flow cytometric assay and genetic analysis.

OBJECTIVE: X-linked lymphoproliferative syndrome (XLP) type 1 is a rare immunodeficiency, which is caused by mutations in SH2D1A gene. The prognosis of XLP is very poor, and hematopoietic stem cell transplantation (HSCT) is the only curative therapy. We characterized the clinical features and outcome of Japanese patients with XLP-1. METHODS: We used a combination of flow cytometric analysis and genetic analysis to identify XLP-1 and reviewed the patient characteristics and survival with HSCT. RESULTS: We identified 33 patients from 21 families with XLP-1 in Japan. Twenty-one of the patients (65%) who did not undergo a transplant died of the disease and complications. Twelve patients underwent HSCT, and 11 of these (92%) survived. CONCLUSION: We described the clinical characteristics and outcomes of Japanese patients with XLP-1, and HSCT was the only curative therapy for XLP-1. The rapid and accurate diagnosis of XLP with the combination of flow cytometric assay and genetic analysis is important.

Wireless capsule endoscopy in pediatric patients: the first series from Japan.

PURPOSE: The aim of our study was to determine the safety and usefulness of capsule endoscopy (CE) in pediatric patients. METHODS: We prospectively examined children (aged 10-18 years) with suspected small bowel disease and recorded capsule transit times, findings, and complications. RESULTS: We performed 19 CE examinations in 12 patients (median age 11.8 years; range 10-18 years). One of the two patients with obscure gastrointestinal bleeding (OGIB), a 14-year-old girl whose OGIB occurred after cord-blood transplantation due to leukemia, was diagnosed with thrombotic microangiopathy. Repeated CE allowed visualization of real-time mucosal changes, such as the improvement of ulcers and bleeding, and newly emerged lymphangiectasia, without causing the patient physical and mental stress. This information facilitated both subsequent evaluation of the clinical course and determination of the appropriate treatment strategy. In the second patient with chronic OGIB, a 10-year-old girl, the detection of severe ileal stenoses by capsule retention led to the diagnosis of non-specific multiple ulcers of the small intestine. After ileal resection, repeated CE detected the recurrence of multiple ulcers and enabled the optimal treatment strategy to be applied. CE confirmed small bowel involvement in a patient with unresponsive Crohn's disease (CD) and excluded CD in all five patients with suspected CD. Similarly, CE confirmed the absence of small bowel involvement in three of the four patients with recurrent abdominal pain, although one patient had nodular lymphoid hyperplasia. CONCLUSIONS: Based on our results, CE is a valuable tool in the differential diagnoses of small bowel diseases, and repeated examination can provide real-time information that will enable evaluation of the clinical course in pediatric patients.

Retrospective analysis of non-anaplastic peripheral T-cell lymphoma in pediatric patients in Japan.

BACKGROUND: Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in pediatric patients are relatively rare. PROCEDURE: We performed a retrospective analysis in patients with PTCL over an 18-year period (1991-2008). RESULTS: We could analyze clinical data in 21 patients with non-anaplastic PTCL; 10 were female and 10 male. Median age of onset was 11 years (range: 1-21 years). There were nine patients with PTCL, not otherwise specified (PTCL-NOS); ten with extranodal NK/T-cell lymphoma, nasal type; one with angioimmunoblastic T-cell lymphoma; and one with subcutaneous panniculitis-like T-cell lymphoma. Initial lesions involved cervical lymph nodes in five patients, and the skin in five patients. In five patients, hemophagocytic syndrome (HPS) was the initial clinical feature. There were 12 patients with advanced stage disease (stages III and IV). Chemotherapy and radiation was administered in 18 and 2 patients, respectively. Among the two patients who did not receive chemotherapy and radiation, one patient died while being treated for HPS but another improved spontaneously. Although 5 patients relapsed, 18 of 21 patients remained alive without disease at last follow-up. Five-year overall survival rate was 85.2%. CONCLUSIONS: Generally, the outcome results of conventional chemotherapy for high-risk PTCL are poor in adult patients. However, the excellent results in our study suggest that PTCL of childhood is quite different from that of adulthood. Although this study is first report about PTCL of Asian children, the number of patients was small in this study. Larger studies are needed to confirm these findings.

Evaluation of apolipoprotein E secretion by macrophages in type 2 diabetic patients: role of HDL and apolipoprotein A-I.

It has been shown that apolipoprotein A-I (ApoA-I) stimulates the secretion of apolipoprotein E (ApoE) from human macrophages. ApoA-I is a major protein constituent of HDL which because of its role in reverse cholesterol transport, has been implicated in the prevention of atherosclerosis. We herein investigated the ability of monocyte-derived macrophages (MDMs) in 42 patients with type 2 diabetes to secrete ApoE; these patients commonly have low plasma HDL and ApoA-I levels. Our data showed that ApoE secretion from these cells was reduced in patients with low plasma HDL and ApoA-I levels; there were positive correlation between ApoE secretion from MDMs and plasma HDL (r2=0.33, p=0.03) and ApoA-I (r2=0.31, p=0.03). Furthermore, we found that ApoE secretion increased concomitantly with an increase in HDL or ApoA-I in treated diabetics (n=24) from 1.99+/-1.86 to 3.40+/-1.77 ng/mg cell protein. These findings suggest another possible link between HDL and ApoA-I metabolism and atherosclerosis in patients with type 2 diabetes.

An infant with idiopathic orbital myositis poorly responsive to steroid therapy: a case report.

A 9-month-old girl developed subacute limited adduction of the left eye, presenting with blepharoptosis. An orbital magnetic resonance imaging (MRI) 2 months after the onset revealed swelling of the left lateral rectus muscle, with increased intensity on T2-weighted images with fat saturation, which was enhanced with gadolinium. She was diagnosed with idiopathic orbital myositis based on history, physical examination, and MRI findings. Swelling of the left lateral rectus muscle was partially reduced by pulse steroid therapy. This is the first reported case of an infant orbital pseudotumor with clinical and MRI findings consistent with subacute orbital myositis. We propose that a fibrotic change of the orbital muscle may occur during a subacute course and would be incompletely responsive to steroid therapy.

Confirming or excluding the diagnosis of Wiskott-Aldrich syndrome in children with thrombocytopenia of an unknown etiology.

Early diagnosis is an important factor in a better prognosis in patients with Wiskott-Aldrich syndrome (WAS), but it is not always easy to distinguish between WAS and immune thrombocytopenic purpura on clinical grounds. To confirm or to exclude a WAS diagnosis promptly for children with thrombocytopenia, the authors performed flow cytometric screening of Wiskott-Aldrich syndrome protein (WASP) for 10 children with thrombocytopenia of an unknown etiology. Five children were diagnosed with WAS, and the remaining 5 were diagnosed as having non-WAS causes of thrombocytopenia. There were no ambiguous results, and these were confirmed by genetic analysis. The authors conclude that screening by flow cytometry for WASP is recommended for boys with persistent thrombocytopenia of an unknown etiology.

Quantitative analysis of apolipoprotein E secretion by human monocyte-derived macrophages in culture.

Apolipoprotein E (apo E) has an impact on lipid metabolism and its production by macrophages is considered to play a protective role against atherosclerosis. Apo A-I stimulates secretion of apo E from macrophages. We developed a new method to evaluate the ability of human monocyte-derived macrophages to secrete apo E, and the effects of factors such as apo A-I were examined. Monocytes separated from peripheral venous blood were cultured. The levels of apo E in macrophage-conditioned medium were quantified by immunoblotting with an anti-human apo E antiserum conjugated with alkaline phosphatase. The basal levels of apo E secretion and the response to exogenous apo A-I in macrophages from 10 healthy volunteers were measured. Sufficient accuracy and sensitivity were confirmed and coefficient of variation of the method was 18 +/- 11% (n = 10). It was confirmed that macrophage secreted apo E in a concentration-dependent manner in response to M-CSF and apo A-I. The average apo E concentration in the conditioned medium of macrophages from 10 healthy subjects was 30.9 +/- 14.7 ng/mg cell protein. After the addition of apo A-I, the average apo E concentration increased, by about 60%, to 49.4 +/- 29.7 ng/mg cell protein (p < 0.05). There was a positive correlation between the apo A-I-induced increase and plasma LDL cholesterol levels (r = +0.54, p < 0.05).

Successful cord blood stem cell transplantation for myelodysplastic syndrome with Behçet disease.

A 10-year-old girl who had been treated as an outpatient for neurofibromatosis type 1 was admitted with fever, 10% weight loss, and abdominal pain that had persisted for 1 month. The clinical manifestations and the results of endoscopy led to the diagnosis of intestinal Behçet disease. Blood cell dysplasia appeared during the hospitalization. The patient subsequently developed blast cells, and the diagnosis of myelodysplastic syndrome (MDS) was made. Behçet disease was first controlled with steroids and diet followed by chemotherapy and cord blood stem cell transplantation (SCT). Both the MDS and Behçet disease went into remission after transplantation. The use of hematopoietic SCT has the potential not only to cure but also to help explicate the mechanism of Behçet disease.