Clinical results of proton beam therapy for advanced neuroblastoma.

PURPOSE: To evaluate the efficacy of proton beam therapy (PBT) for pediatric patients with advanced neuroblastoma. METHODS: PBT was conducted at 21 sites in 14 patients with neuroblastoma from 1984 to 2010. Most patients were difficult to treat with photon radiotherapy. Two and 6 patients were classified into stages 3 and 4, respectively, and 6 patients had recurrent disease. Seven of the 8 patients who received PBT as the initial treatment were classified as the high risk group. Twelve patients had gross residual disease before PBT and 2 had undergone intraoperative radiotherapy before PBT. Five patients received PBT for multiple sites, including remote metastases. Photon radiotherapy was used in combination with PBT for 3 patients. The PBT doses ranged from 19.8 to 45.5 GyE (median: 30.6 GyE). RESULTS: Seven patients are alive with no evidence of disease, 1 is alive with disease progression, and 6 died due to the tumor. Recurrence in the treatment field was not observed and the 3-year locoregional control rate was 82%. Severe acute radiotoxicity was not observed, but 1 patient had narrowing of the aorta and asymptomatic vertebral compression fracture at 28 years after PBT, and hair loss was prolonged in one patient. CONCLUSION: PBT may be a better alternative to photon radiotherapy for children with advanced neuroblastoma, and may be conducted safely for patients with neuroblastoma that is difficult to manage using photon beams.

Matrix metalloproteinase-9 expression in congenital diaphragmatic hernia during mechanical ventilation.

PURPOSE: Matrix metalloproteinase-9 (MMP-9) is detected in lung tissues subjected to ventilator-induced injury and is involved in the process of lung injury. We investigated the immunohistochemical expression of MMP-9 in the bilateral lungs of newborns with congenital diaphragmatic hernia (CDH) during mechanical ventilation and evaluated the degree of damage based on MMP-9 expression. METHODS: Lung tissue samples were obtained during autopsy from six newborns with CDH. Control lung tissue samples were obtained from two of these newborns; one who died of persistent pulmonary hypertension after being ventilated for 2 days, but whose bilateral lungs were not subjected to the compressions of herniation, and one who died of bilateral diaphragmatic hernias soon after birth, but was not subjected to artificial ventilation. The other four newborns with CDH had unilateral Bochdalek hernias. Immunohistochemical detection of MMP-9 expression was done using a wet autoclave antigen retrieval method on sections from formalin-fixed and paraffin-embedded lung tissue. RESULTS: The reaction and distribution of MMP-9 was strongly positive in the alveolar macrophages in thickened alveolar septi and ducts, and in the inflammatory cells around the parenchymal hemorrhage and intra-alveolar spaces. Only the four patients with unilateral Bochdalek hernia had widely positive MMP-9 immunoreactivity in the unaffected side, as well as the affected side. CONCLUSIONS: Based on MMP-9 expression, the lungs of newborns with CDH were damaged bilaterally during mechanical ventilation.

A case of pediatric ovarian dysgerminoma associated with high serum levels and positive immunohistochemical staining of neuron-specific enolase.

A 5-year-old girl presented with a painful abdominal mass. Abdominal magnetic resonance imaging (MRI) showed 3 separate masses. Tumor markers including lactate dehydrogenase (LDH), cancer antigen-125 (CA-125), beta-subunit of human chorionic gonadotropin (beta-hCG) and neuron-specific enolase (NSE) were elevated. At operation, the main tumor arose from the left ovary and was associated with torsion, whereas the other lesions were lymph node metastases. A salpingo-oophorectomy was performed. Histopathologic examination indicated that the tumor was a dysgerminoma. Immunohistochemicallly, the cells were positive for NSE and placental alkaline phosphatase (PALP) but were negative for CA-125, beta-hCG, S-100, glial fibrillary acidic protein, and vimentin. The elevated serum levels of tumor markers improved dramatically after the operation and chemotherapy.

Clinical significance of measurement of resting energy expenditure in childhood.

1. Biliary atresia (BA), as a common disease in Japan, and cystic fibrosis (CF), as an extremely uncommon disease in Japan, were selected to assess the clinical significance of measurement of energy expenditure (EE). 2. Energy expenditure was significantly higher in children with BA than in normal children. 3. Measurement of EE in BA lead to clues to resolving its mechanism by novel assessment of interleukin-6 and leptin. 4. Energy expenditure in children with CF is also higher, but this has been addressed by nutritional intervention with additional calories. 5. Individualization of EE measurement is necessary in the analysis of pathological mechanisms and nutritional management of patients with both common and uncommon diseases.

Accuracy of flow and sensors of indirect calorimetry for neonates and infants: using mass spectrometry and a pneumotachogram.

1. The accuracy of measurements of flow rate and concentrations of O2 and CO2 in expiratory gas by indirect calorimetry (IC) using paediatric and adult circuits were assessed by mass spectrometry and a pneumotachogram, which have been proven as the most reliable instruments for these purposes. 2. In the paediatric circuit, all measurements were demonstrated to be reliable: error rates for flow rate, O2 concentration and CO2 concentration were +3.13, +2.66 and -6.63%, respectively. All were within the 10%, which is acceptable as a biological error. 3. However, in the adult circuit of IC, all measurements were reliable except for measurements of CO2 concentration: error rates for flow rate, O2 concentration and CO2 concentration were +2.82, +1.64 and +11.42%, respectively. 4. A fluctuation phenomenon of expiratory gas concentration was observed only in IC. Mass spectrometry did not show this phenomenon. This phenomenon seems to be derived from the IC machine itself.

Accuracy of flow and sensors of indirect calorimetry for neonates and infants: Using mass spectrometry and a pneumotachogram.

1. The accuracy of measurements of flow rate and concentrations of O2 and CO2 in expiratory gas by indirect calorimetry (IC) using paediatric and adult circuits were assessed by mass spectrometry and a pneumotachogram, which have been proven as the most reliable instruments for these purposes. 2. In the paediatric circuit, all measurements were demonstrated to be reliable: error rates for flow rate, O2 concentration and CO2 concentration were +3.13, +2.66 and -6.63%, respectively. All were within the 10%, which is acceptable as a biological error. 3. However, in the adult circuit of IC, all measurements were reliable except for measurements of CO2 concentration: error rates for flow rate, O2 concentration and CO2 concentration were +2.82, +1.64 and +11.42%, respectively. 4. A fluctuation phenomenon of expiratory gas concentration was observed only in IC. Mass spectrometry did not show this phenomenon. This phenomenon seems to be derived from the IC machine itself.

CLINICAL SIGNIFICANCE OF MEASUREMENT OF RESTING ENERGY EXPENDITURE IN CHILDHOOD.

1. Biliary atresia (BA), as a common disease in Japan, and cystic fibrosis (CF), as an extremely uncommon disease in Japan, were selected to assess the clinical significance of measurement of energy expenditure (EE). 2. Energy expenditure was significantly higher in children with BA than in normal children. 3. Measurement of EE in BA lead to clues to resolving its mechanism by novel assessment of interleukin-6 and leptin. 4. Energy expenditure in children with CF is also higher, but this has been addressed by nutritional intervention with additional calories. 5. Individualization of EE measurement is necessary in the analysis of pathological mechanisms and nutritional management of patients with both common and uncommon diseases.