[Clinical experience with a case of Sipple syndrome].
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Biomedical subjects
Publications and source records attributed to J Takayama.
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Thirty-one patients with acute non-lymphocytic leukemia (18 patients) or with high-risk refractory acute lymphocytic leukemia (13 patients) underwent bone marrow transplantation between March 1980 and March 1990. The high-dose conditioning regimen employed included cyclophosphamide followed by fractionated total body irradiation (12 GY). Fourteen patients who had an HLA-identical sibling donor received allogeneic bone marrow transplantation (allo-BMT); the other 17 patients received autologous bone marrow transplantation (auto-BMT) purged with 4-hydroperoxycyclophosphamide (4HC). Four of the 14 allo-graft recipients died of leukemic relapse and 2 others died of graft-versus-host disease. Three of the 17 auto-graft recipients died of relapse and 1 suffered relapse in the testes. The actuarial risk of relapse was 29% for the allo-BMT patients and 24% for the auto-BMT patients (P less than 0.05). The event-free survival rate at five years was 57% and 74% respectively (P less than 0.05). Although there was no difference between them, a trend toward a higher survival rate and a lower mortality and morbidity was observed in the auto-BMT group. These results suggest that autologous bone marrow transplantation purged with 4HC is an effective and useful treatment for children with acute non-lymphocytic and lymphocytic leukemia who have no HLA-identical donor.
A twenty-four-year-old male patient with stage III advanced extragonadal germ-cell tumor obtained complete remission after comprehensive treatment including high-dose combination chemotherapy with autologous bone marrow transplantation. He had massive tumors in cervical, mediastinal, abdominal and inguinal lymph nodes, bilateral lungs and liver. Ascites, plural effusion and pericardial effusion were also noted. Cancer cells were demonstrated from his bloody sputum, pericardial drainage and an aspirate from supraclavicular tumor. His tumor produced hCG, AFP, placental ALP and LDH, and hCG was the best marker for the diagnosis and monitoring. The initial serum hCG level was high at 460,000 mIU/ml, but fell to 13 mIU/ml after 3 courses of PVP therapy. However, it rose ten-fold in a week. After ultra-high dose combination chemotherapy with autologous BMT, the patient's hCG fell to 1.8 mIU/ml and remained at that level thereafter. He has remained well with no sign of recurrence after 25 months.
A retrospective clinicopathological study was performed on 149 patients who developed malignant lymphoma at under 20 years of age and were diagnosed and treated at the National Cancer Center Hospital between 1962-1986. Using the Japanese Lymphoma Study Group classification (and Working Formulation), we reclassified the 84 evaluable tissue specimens as follows: follicular large and mixed lymphoma (two cases), diffuse lymphoblastic lymphoma (40 cases), Burkitt's lymphoma (small noncleaved, SNC) (12 cases), diffuse large and mixed cell lymphoma (25 cases), and unclassified (five cases). The age of the patients ranged from 6 months to 20 years, with a median of 11 years. The clinical characteristics were found to depend upon the histological diagnosis, as reported previously. To evaluate the influence of various clinical and morphological parameters on survival, univariate analysis was performed for each histological subtype. In lymphoblastic lymphoma, patients with a mediastinal mass had significantly earlier development of leukemic conversion and a shorter survival than patients without a mass. Because of the small number of patients and their short survival, no significant prognostic factors were found in Burkitt's lymphoma (SNC). In large and mixed cell lymphoma, response to therapy was the most significant prognostic factor. As therapy became more intense and systematic throughout the study period, the complete remission rate and survival improved steadily. Autopsy findings confirmed that lymphoblastic lymphoma and Burkitt's lymphoma (SNC) spread systemically earlier than large and mixed cell lymphoma.
A 17-year-old male patient with T-cell type lymphoblastic lymphoma in complete remission underwent high dose chemotherapy (busulfan 16 mg/kg and cyclophosphamide 120 mg/kg) followed by autologous bone marrow transplantation (ABMT). The patient had been taking oral acyclovir (200 mg x 5) daily from seven days prior to the ABMT (day -7). On day +24, he complained of epigastralgia and general malaise, and the next day his GOT and GPT rose to 570 U/l and 397 U/l, respectively. Although he had no mucocutaneous lesions, hepatitis caused by a herpes virus was suspected, and high dose intravenous acyclovir (10 mg/kg x 3/day) was immediately started. His GOT, GPT and total bilirubin reached peaks of 2,870 U/l on day +26, 1,830 U/l on day +27 and 10.3 mg/dl on day +39, respectively, and rapidly improved thereafter. Serological analyses on IgG antibody titers to herpes simplex virus type 1 using an enzyme-linked immunosorbent assay revealed specific increases (454-fold before transplantation to 3,830-fold on day +46). Antiviral antibody titers to cytomegalovirus, varicella-zoster virus and Epstein-Barr virus showed no significant changes. The serologic markers of hepatitis B virus, hepatitis A virus and hepatitis C virus were all negative. The results indicate the patient's severe icteric hepatitis to have been caused by a reactivation of herpes simplex virus type 1 due to immunosuppression after high dose chemotherapy with ABMT. It is suggested that prompt commencement of high dose intravenous acyclovir is required to treat severe herpes simplex virus hepatitis affecting immunocompromised patients.
Complete resection of a rare hepatoblastoma in the caudate lobe, involving the inferior vena cava (IVC), is reported. After systemic chemotherapy, a 5-year-old child underwent exploratory laparotomy at another hospital, but resection was not attempted because the tumor in the caudate lobe had extensively invaded the retrohepatic IVC. However, because not only the lack of distant metastases but also the establishment of extrahepatic collaterals were confirmed by imaging, we thought it was possible to radically resect the tumor. We successfully performed an extended left hepatic lobectomy including total excision of the caudate lobe and the involved portion of the IVC. Although we did not reconstruct the IVC, no clinical manifestations arising from caval congestion were seen. The serum alpha-fetoprotein value declined below the normal limit. Our experience with this case has introduced a radical resectability for hepatic malignancy in the caudate lobe, even if it has extended into the IVC.
One hundred four children with infection accompanying hematologic disorders and solid tumors were treated with aztreonam (AZT) (120-150 mg/kg), either alone or in combination with one of the following drugs; cefmetazole (CMZ) (120-150 mg/kg), piperacillin (PIPC) (120-150 mg/kg), or amikacin (AMK) (5-10 mg/kg). The overall efficacy rate was 69.2%. Efficacy rates by regimen were as follows: AZT alone was 63.2%, AZT plus CMZ was 73.6%, AZT plus PIPC was 74.1% and AZT plus AMK was 20.0%. Efficacy rates in different types of infections were 53.2% for sepsis and suspected sepsis, 78.9% for pneumonia and respiratory tract infection, 93.1% for fever of undetermined origin and 55.6% for other infections. The efficacy rate was 71.3% in 94 patients in whom causative organisms were not identified and 50.0% in 10 patients in whom causative organisms were identified. Most of infections in which causative organisms were identified were caused by Gram-negative pathogens. The response rate among infections caused by Gram-negative bacilli was 50.0%. A combination of AZT and CMZ or PIPC was effective in 3 (100.0%) out of 3 patients in whom Escherichia coli was the causative organism. Efficacies classified according to different neutrophil counts were 59.3% for less than or equal to 100/microliters, 78.6% for 101-500/microliters and 82.4% for greater than or equal to 501/microliters. No significant adverse reactions were observed. These results indicated that combination of AZT and 2nd generation cephalosporins or penicillins were well tolerated and effective for infections complicated with accompanying hematologic disorders and solid tumors.
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Twenty two cases with Hodgkin's disease under 20 years of age who were diagnosed and treated in National Cancer Center during 1962-1986 were studied retrospectively. The most common initial symptom was swelling of lymph nodes (86%) and only 5 cases (23%) showed "B" symptoms. Laboratory findings showed that there were some cases with increased WBC counts but only 2 cases with an elevated LDH value. In 2 out of 4 cases serum copper value correlated well with their clinical state. Histologically lymphocyte predominance type, mixed cellularity type and nodular sclerosis type almost equally occurred in children younger than age 15 years. On the other hand nodular sclerosis type with mediastinal mass was predominantly encountered in older patients (especially female). The ten years' survival rate in stage I and II patients was 59% compared with 21% in stage III and IV patients. As for the results of initial treatment, complete remission and 10 years' survival rate were 91% and 87% in recent 12 years (1975-1986) compared with 55% and 36% in the preceding 13 years (1962-1974) respectively. Autopsy findings revealed rare involvements of the central nervous system and kidneys. Various late effects which may be caused by escalating doses of radiotherapy occurred in 6 out of 9 cases under the age of 15 years who survived. On the basis of these results lower-doses of radiotherapy combined with systemic chemotherapy appeared to be advisable for the treatment of childhood Hodgkin's disease.
Four patients with osteosarcoma were treated with intensive chemotherapy and autologous bone marrow transplantation (ABMT). The patients received high-dose methotrexate (9-12 mg/m2) with citrovorum factor rescue, high-dose melphalan (60 mg/m2 X 3), actinomycin D (0.5 mg/m2 X 3), adriamycin (30 mg/m2 X 2) and high-dose cyclophosphamide (60 mg/kg X 2) during 4 weeks. Bone marrow was aspirated and cryopreserved before treatment and reinfused 48 hours after the completion of chemotherapy. Two of four patients had advanced osteosarcoma with multiple pulmonary metastasis, one of whom had responded well and achieved partial response while the other had shown no response, and both patients died of disease progression 4 and 11 months after ABMT, respectively. The other two patients who received this regimen at an earlier disease stage for prevention of pulmonary metastasis, are alive and well without any evidence of metastasis 31 and 18 months after ABMT, respectively. This regimen was tolerated well in all patients except for mild nausea and vomiting. No infectious episodes were observed during the period of aplasia which continued for 19 to 38 days after marrow infusion. These results suggest that this supralethal combination chemotherapy is safe and tolerable when used with ABMT and effective for patients with osteosarcoma, especially when applied in the non-metastatic phase.
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N-myc, which has partial sequence homology to the oncogene c-myc, was isolated from human neuroblastoma cell lines. We have surveyed amplification of N-myc, clone 8 and pG21 in human neuroblastoma cell lines, xenografts and in primary tumors and found that amplification frequently occurred in tumors classified as stage III and IV. In situ hybridization studies demonstrated that in neuroblastomas, chromosome aberrations such as HSR (homogeneously staining region) and DMs (double minutes) are cytological manifestations of the amplification of these clones. The N-myc-related gene seems to contribute to cell growth or differentiation of the nerve cell and its amplification with enhanced expression promotes the progression of the tumor with poor prognosis.
Three children with acute nonlymphocytic leukemia in first remission were given cyclophosphamide (60 mg/kg on each of 2 days), fractionated total-body irradiation (total 12 Gy, six fractions), and a marrow transplant from an HLA-identical, mixed lymphocyte culture-negative sibling. All three patients are alive in a leukemia-free state 12 to 25 mo after transplantation. There were very few complication, other than mild graft-versus-host disease that developed in two patients. No interstitial pneumonitis and no serious infections have occurred. Long-term disease-free survival is expected in these patients.
Alpha and beta interferon were tested for antitumor activity and clinical toxicity in 15 children suffering from cancer. The drug was administered IV, IM, IT or intralesionally daily in the majority of cases in total doses of 18 X 10(6) to 9,634 X 10(5) IU. Major toxicities were a flulike syndrome, elevation of transaminase activity and leukopenia. A minor response (less than 50%) was observed in one patient with glioblastoma, treated by intrathecal administration, and an objective local response was noted in one rhabdomyosarcoma patient with multiple subcutaneous metastases, who was treated by intralesional administration. CNS leukemia in two patients improved without hematological response. Further trials are warranted.
A new unstable hemoglobin was discovered in a Japanese boy without any signs of hemolytic disease during screening of patients by the isopropanol test. The abnormal hemoglobin was found in three generations. This slightly unstable hemoglobin could not be separated from Hb A by electrophoresis. All carriers showed an increased whole blood oxygen affinity. Structural studies demonstrated a previously unreported amino acid substitution, beta 23[B5] valine substituting for glycine. This new unstable variant has been named Hb Miyashiro.
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