Tetsuo Hashida

Neuroblastoma. Mass screening for early detection and its prognosis.

Since July 1973, the authors began developing a mass screening system using a VMA (vanilmandelic acid) spot test on 6‐to‐7 month‐old infants for early detection of neuroblastoma in Kyoto city, Japan. Using this method, six infants with this tumor were discovered; five of the six infants were cured, and one is under treatment. These patients showed a favorable prognosis on early diagnosis. in this article, 57 neuroblastoma patients from the Department of Pediatrics, Kyoto Prefectural University of Medicine, treated during the last 20 years, from July 1962 to June 1982, are evaluated. Since the mass screening program has run smoothly since July 1974, clinical findings are compared between 35 neuroblastoma cases before mass screening from the 12‐year period from July 1962 to June 1974 and 22 cases after mass screening, during the 8‐year period from July 1974 to June 1982. Before mass screening, only 20% (7/35) of the patients were discovered with neuroblastoma younger than 12 months of age and 68.6% were older than 2 years of age. After mass screening, 54.6% (12/22) of the patients were younger than 12 months of age and only 31.8% (7/22) were older than 2 years of age. Before mass screening, 17.1% (6/35) survived with five of the six surviving patients being younger than 12 months of age at the time of diagnosis; 72.7% (16/22) of the patients detected after mass screening are living now. Eleven of the 16 patients have already been cured, and the remaining 5 patients are presently undergoing treatment. A marked improvement of their prognoses is dependent on the early detection of this tumor by mass screening. To date, using the VMA spot test for early detection in infancy is convenient and effective for improvement of its prognosis.

Management of severe neutropenia with cyclosporin during initial treatment of Epstein-Barr virus-related hemophagocytic lymphohistiocytosis

Severe neutropenia (absolute neutrophil count <500/μ1) is probably due to the combined effects of dysregulated cytokine production and chemotherapeutic agents, and is one of the risk factors in the initial treatment of patients with Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). We report here 9 cases of neutropenic HLH, of which 8 were treated with cyclosporin (CSA, 2-6 mg/kg/day; continuous infusion, or 6mg/kg/day; per os, for periods ranging from 9 days to 8 weeks) in the initial neutropenic phase during induction treatment using corticosteroids and etoposide. Five of the 6 cases, in which CSA treatment was started early (before the second week of induction), survived the critical period with recovery of neutrophil counts within a week. The remaining 3 cases, in which CSA was introduced later or not at all, died of infection. Based on these results, we recommend a prompt short-term CSA infusion during neutropenic episodes in the most common treatment regimen of etoposide and corticosteroids in patients with HLH. Improved neutrophil recovery as a result of CSA treatment makes it possible to continue immunochemotherapy safely and obtain improved patient outcomes.

Malignant histiocytosis in childhood: Clinical features and therapeutic results by combination chemotherapy

Ten children, four males and six females, with malignant histiocytosis were treated from July 1980 to July 1984. None of them had an affected sibling with a similar disorder. Septic-type fever, hepatosplenomegaly, lymphadenopathy, pulmonary infiltration, and disseminated intravascular coagulation were common signs and symptoms, and convulsion occurred in four cases. The diagnosis was made from bone marrow smears in all cases. In five cases, biopsy or autopsy specimens confirmed the diagnosis. In five cases studied, proliferating histiocytes in lymph nodes were demonstrated to be S100 protein-positive. All patients were treated with adriamycin, cyclophosphamide, vincristine, and prednisone (ACOP). Complete response was achieved in four patients after two to three courses of ACOP, and another case attained complete remission after further drug treatment. The five complete responders are now alive without evidence of disease after 23-48 months from the onset. Among partial and no responders, four died within 3 months and one has been alive with disease for 2 months. Bone marrow aspiration is useful for prompt diagnosis, and early treatment with intensive combination chemotherapy improves the prognosis of malignant histiocytosis in childhood.

Therapeutic effects of human leukocyte interferon on chronic active hepatitis B in children

Seven children with chronic active hepatitis (CAH) and one child with persistently abnormal results of liver function tests due to hepatitis B virus (HBV) infection were treated with human leukocyte interferon (Hu-IFN). Five of them were positive for eAg and two of the three who were measured for DNA polymerase (DNAP) activity in sera showed moderate elevations of its levels. Hu-IFN was injected intramuscularly daily or once weekly at doses of 0.05–1 x 106 IU. The total dose per patient varied from 10.5–54 x 106 IU. After administration of Hu-IFN, rapid loss of eAg was observed in two of the five eAg patients, and DNAP activity reverted to normal ranges in the two patients with moderate elevations of its levels. One of the patients who lost eAg has retained normal serum glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels for more than 2 years after therapy with Hu-IFN. Serial hepatic biopsies were performed in only one patient. In the second biopsy, 3 months after therapy with Hu-α-IFN, infiltration of inflammatory cells in the portal region was improved compared with earlier findings. Immediate and/or prolonged adverse side effects were not observed during or after administration of Hu-α-IFN. For the present, we propose these six conditions for use of Hu-α-IFN in children with HBV infection. Children should: (a) be more than 1 year old; (b) have abnormal liver function for more than 6 months; (c) have a liver biopsy demonstrating CAH; (d) have moderate elevation of DNAP activity; (e) be eAg positive; and (f) be unresponsive to other treatments.