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Biomedical subjects

F Bessho

Publications and source records attributed to F Bessho.

At least 19 recordsLinked to original sources

Mass screening in Japan increased the detection of infants with neuroblastoma without a decrease in cases in older children.

Analysis of data from the Kanto-Ko-Shin-Etsu Branch of the Japan Children's Cancer Registry revealed that mass screening for neuroblastoma increased the detection of cases in infants younger than 1 year from about 25% before screening to about 50%, and the percentage of neuroblastomas among all pediatric cancers almost doubled, from approximately 10% to 19.3%. However, when the cases found on screening were subtracted, the numbers after the onset of mass screening were similar to those before screening. It is likely that neuroblastoma mass screening has identified a unique type of tumor, which may not be recognized without mass screening, rather than that it has contributed to the earlier diagnosis of tumors in older children.

Age Factors

Malignant cell detection in Burkitt's lymphoma using third-complementarity-determining region (CDRIII), clone-specific probe developed by sequencing DNA from stored slides.

The DNA sequence of the third-complementarity-determining region (CDRIII) of the immunoglobulin heavy chain (IgH) gene in a case of Burkitt's lymphoma was determined by polymerase chain reaction (PCR) using template DNA extracted from a smear stored at room temperature for more than one year. The DNA sequence obtained from the stored slide was compared with that of DNA from a frozen lymph node biopsied at the initial presentation. The sequences were shown to be identical, implying that DNA from a smear on a stored slide can be used as a source of DNA for PCR amplification, sequencing, and development of a clone-specific probe. Using oligonucleotides generated from one of the CDRIII sequences of the IgH gene as molecular probes, a retrospective study for the malignant clone on the smears was carried out. Malignant cells were detectable in the peripheral blood at an early stage of bone marrow relapse but not in the peripheral blood or bone marrow at the initial presentation. No malignant clone was detected in the bone marrow when testicular infiltration was diagnosed by examination of a pathological specimen. Thus, the technique permits molecular analysis of hematologic malignancies of B-cell lineage in cases where fresh or frozen specimens are not available.

Base Sequence

Improved prognosis of acute nonlymphocytic leukemia in children: results of the 12th-ANLL protocol of Tokyo Children's Cancer Study Group.

Thirty-one children with ANLL were treated using the 12th-ANLL Protocol of the Tokyo Children's Cancer Study Group incorporating an ACMP 2-step regimen. Induction therapy consisted of two 4-day courses of adriamycin (ADR) and cytosine arabinoside (ARA-C) given with a 7-day interval. Those patients who achieved remission were given one more course as early intensification. Late intensification consisted of a 5-day course of ARA-C and one dose of ADR which was repeated until the cumulative dosage of ADR reached 465 mg/m2. After this point, treatment was divided into 2 courses. Both courses included ARA-C and one course had achlacinomycin in addition. Twenty-seven children (87%) attained remission after one or two courses of induction therapy. Kaplan-Meyer analysis revealed that the continuous complete remission rate and event-free survival were 71% and 51%, respectively, 5 years after diagnosis. Toxicity was minimum with only one death during the remission. These results are encouraging and warrant further trials.

Adolescent

Late effects of childhood acute leukemia and its treatment.

Late effects of childhood acute leukemia and its treatment were studied in 776 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.

Adolescent

Treatment of acute lymphoblastic leukemia in the Tokyo Children's Cancer Study Group--preliminary results of L84-11 protocol.

The Tokyo Children's Cancer Study Group (TCCSG) has performed prospective randomized controlled studies since 1984 for childhood acute lymphoblastic leukemia (ALL). Four hundred and ninety-eight newly diagnosed patients were treated with 5 different regimens designated as S1, S2 for a standard risk group (SRG), H1 and H2 for a high risk group (HRG) and HEX for an extremely high risk group of patients. We added intermediate-dose methotrexate as early intensification therapy in the S2 and H2 groups to reduce extramedullary and medullary relapses. Event-free survival of all patients at 4 years 6 months from the start of this regimen (median follow-up period 32 months) was 67.5%. The CNS relapse rate was significantly decreased to 2.2% compared to previously reported studies and our own experience. There were some unexpected complications of the CNS such as myelopathy and/or leukoencephalopathy. For the SRG early ID-MTX seemed to be useful to improve the prognosis, but triple intrathecal injections (TIT) should be limited in number. The 24Gy cranial irradiation (CRX) was effective but possibly excessive for the HRG. As evidenced by the success of the HEX group regimen, more intensive multi-drug consolidation in the early post-remission phase might be necessary to improve further the prognosis and to make it possible to shorten the treatment periods.

Antineoplastic Combined Chemotherapy Protocols

Clonal analysis of transient myeloproliferative disorder in Down's syndrome.

Three Down's syndrome patients with transient myeloproliferative disorder were studied for clonality of the proliferating blast cells using the X chromosome-linked polymorphic gene phosphoglycerate kinase, immunoglobulin heavy chain (IgH) gene and T-cell antigen receptor (TCR) (beta, gamma, delta) genes. None of the three cases showed rearrangements of IgH, TCR beta, gamma, or delta genes, indicating the non-lymphoid nature of the proliferating blast cells. The X chromosome inactivation pattern showed that the cells in the blast population in all of the three cases of transient myeloproliferative disorder were clonal. These data suggest that at least some of this disorder can be due to a spontaneously regressing clone of malignant cells.

Adolescent

[Acute nonlymphocytic leukemias with 21 trisomy as a sole anomaly].

Two cases of childhood acute nonlymphocytic leukemia (ANLL) with 21 trisomy as a sole cytogenetic change are reported. The first case was a 4-year-old boy with FAB-M5a. 47, XY, +21 was found in 7 of 12 metaphases at diagnosis and in all 15 metaphases examined at relapse 4 years and 3 months later. The second case was a 14-year-old boy with FAB-M1, all 20 cells examined showed 21 trisomy at diagnosis. His peripheral blood in remission revealed normal male karyotype. Although 21 trisomy is relatively common in ANLL of children, 21 trisomy as a sole anomaly is extremely rare, and to our knowledge, only 2 cases (19 included adult cases) have previously been reported.

Adolescent

Acute non-lymphocytic leukemia is not a major type of childhood leukemia in Japan.

The distribution of acute leukemia according to type was examined in Japanese children by three surveys: (1) a review of bone marrow slides of 81 cases diagnosed as acute myelogenous leukemia between 1964 and 1976; (2) a prospective study of 97 cases observed since 1977, and (3) a study of 8108 cases registered with the Children's Cancer Registry of Japan from 1969 to 1984. The results indicate that the ratio of acute lymphocytic leukemia to non-lymphocytic leukemia in Japan is not different from that in other countries.

Child

Chronic myelomonocytic leukemia with chromosomal changes involving 1p36 and hepatocellular carcinoma in a case of Fanconi's anemia.

A girl with Fanconi's anemia developed chronic myelomonocytic leukemia and hepatocellular carcinoma. At the time that chronic myelomonocytic leukemia was diagnosed, all metaphases of the bone marrow cells revealed a chromosomal translocation involving 1p36. It is suggested that the occurrence of this rare type of leukemia in our patient is related to the chromosomal translocation.

Anemia, Aplastic

[Cytological findings of the cerebrospinal fluid at diagnosis of acute lymphocytic leukemia in children--effect of remission induction chemotherapy].

Cytological examination of the cerebrospinal fluid (CSF) was performed in 88 children with acute lymphocytic leukemia at the time of initial diagnosis (54 cases), during (day 1-15, 17 cases) or after (day 37-58, 17 cases) the remission induction chemotherapy. Leukemic cells were found on cytological examination in 23 cases (42.6%), 5 cases (29.4%) and 2 cases (11.8%), respectively, and the incidence of central nervous system (CNS) leukemia had a tendency to decrease during the induction chemotherapy. The follow-up study of 15 cases of CNS leukemia at diagnosis revealed that the leukemic cells in CSF had decreased within 2 weeks and then disappeared after the induction chemotherapy. These findings indicate the therapeutic effect of induction chemotherapy including prednisolone on subclinical CNS leukemia at diagnosis.

Adolescent

Ultrastructural studies of peripheral blood of neonates with Down's syndrome and transient abnormal myelopoiesis.

Ultrastructural studies were performed on blood samples from five neonates with Down's syndrome and transient abnormal myelopoiesis (TAM). Three methods of fixation were employed to detect diaminobenzidine (DAB) reactivity. The first method used glutaraldehyde solution, while the second and third methods used tannic acid-glutaraldehyde mixtures. Before fixation by the second method, specimens were washed in order to eliminate plasma, and before fixation by the third were diluted to lessen the effects of plasma protein. The latter two methods were more sensitive than the first for detection of DAB reactivity, while the third also resulted in better preservation of morphology than did the second. Even the first method was able to detect DAB reactivity in cells of megakaryocyte-platelet series in appropriate sections. Although the majority of blasts appeared with light microscopy to be undifferentiated, their ultrastructural morphology and ultrastructural cytochemistry were in fact found to be quite heterogeneous, consisting of cells of the megakaryocyte-platelet and granulocytic series, including basophils, and erythroid precursors. This finding supported the view that TAM was the result of unstable hematopoiesis rather than true leukemia.

3,3'-Diaminobenzidine

Cytogenetic findings and clinical features in acute leukemia and transient myeloproliferative disorder in Down's syndrome.

Cytogenetic, immunologic, and electron microscopic studies were performed on the blast cells of 28 pediatric patients with Down's syndrome, 13 with acute leukemia (DS-AL) and 15 with transient myeloproliferative disorders (DS-TMD). Clonal chromosome abnormalities were found in the cells of all patients with DS-AL but not those with DS-TMD. The younger ages and higher hemoglobin concentrations, platelet counts, and WBC counts of DS-TMD patients provided a clinical contrast with the frankly leukemic cases. Myelodysplastic syndrome, characterized by a small percentage of leukemic blast cells, was observed in 11 of the 13 patients with DS-AL compared with none in the DS-TMD group. Electron microscopy disclosed a positive platelet peroxidase reaction in each of the 11 DS-TMD patients and in nine of the 13 DS-AL patients. Immunologic studies revealed antiplatelet-megakaryocyte antigens on the blast cells of the majority of patients in both study groups. Our findings suggest that the blast cells in cases of DS-AL and DS-TMD arise from cells of the megakaryocytic lineage or from a myeloid progenitor with the capacity for megakaryocytic differentiation. The high risk of the development of AL in patients with DS who are less than 3 years old may be related to increased megakaryocyte proliferation in this age group.

Acute Disease

[Clinical evaluation of cisplatin in children with malignant solid tumors. Pediatric Cisplatin Study Group].

A cooperative multicenter clinical study on cisplatin in children with malignant solid tumors was conducted in seventeen institutions. Of 63 children entered into the study, 18 patients were treated with cisplatin alone, 33 with a VCAP regimen (VCR, CPA, ADM and CDDP) and 12 with other combination regimens. The numbers of evaluable patients were 14, 27 and 7, respectively. Response rates for neuroblastoma were 37.5% (3/8) with cisplatin alone and 79.2% (19/24) for the VCAP regimen. Major adverse effects were gastrointestinal symptoms, bone marrow suppression and renal impairment. Hearing difficulty, electrolyte imbalance and transient elevation of transaminase were also observed. However, these adverse effects were within a tolerable range of severity. The results of this study demonstrate that cisplatin is a useful drug in the treatment of neuroblastoma.

Adrenal Gland Neoplasms

Testicular histology and function following long-term chemotherapy of acute leukemia in children and outcome of the patients who received testicular biopsy.

Wedge biopsy of the testis was performed in 46 children who had received long-term chemotherapy for acute lymphoblastic leukemia. Occult testicular infiltration was noted in three children (6.5%). Two of three children with biopsy-proven infiltration died of systemic disease in spite of local irradiation and reinduction chemotherapy. Six of 43 children shown to be negative by testicular biopsy relapsed 11 months to 15 years later, and 3 of 6 patients died of systemic disease, but none of the cases developed testicular disease. Chemotherapy-induced gonadal damage was observed in 30 of 46 children, and tubular damage was occasionally still seen 4 years after cessation of treatment. Although gonadal damage usually depends on the cumulative dosage of cyclophosphamide, intact tubular fertility index was found in several children who had received a greater dose of cyclophosphamide intermittently. Induction and maintenance chemotherapy for acute lymphoblastic leukemia had little influence on hormonal function. Testicular biopsy at the time of cessation of chemotherapy seems to be worthwhile for the subsequent strategy of treatment, and long-term surveillance for gonadal damage of long-term survivors will be required.

Age Factors