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Biomedical subjects

J Okamura

Publications and source records attributed to J Okamura.

At least 55 records · Page 3Linked to original sources

[Liver metastases from breast cancer--clinical features and treatment].

Between 1986 and 1997, we treated 55 patients with liver metastases of breast cancer. In this study, the clinical features and effects of systemic or intra-arterial chemo-endocrine therapy for these patients were reviewed to clarify the characteristics of liver metastases and establish the optimum therapy. One of the 55 patients underwent hepatectomy, 25 were treated with systemic chemo-endocrine therapy [A] and 10 were treated with one-shot intra-arterial chemoembolization through hepatic artery [B] while the other 19 were given hepatic arterial infusion chemotherapy [C]. The response rate in the group [B] and [C] were better than in group [A], whereas there was no significant difference in survival time among the three groups. There were 14 cases (25.5%) among them showing metastasis in the thoracico-abdominal lymph nodes. In these patients, liver metastases seemed to have occurred through the lymphogenic route. In the intra-arterial chemotherapy ([B] + [C]) group, the survival time of patients with metastasis in the thoracico-abdominal lymph nodes was significantly shorter than that of patients without metastasis (p = 0.01). This study suggests that intra-arterial chemotherapy combined with MPA should be effective and useful for advanced breast cancer patients with liver metastases. And for lymphogenic liver metastases, it should be necessary to be combined with more intensive systemic chemo-endocrine therapy.

Antineoplastic Combined Chemotherapy Protocols↗

[PyNPase expression and cancer progression in the colorectum].

We analyzed PyNPase expression discriminating between cancer and tumor stroma of the colorectum by Western blotting using a newly developed extraction method from microdissected tissue sections fixed with buffered formalin. Analysis of 98 colorectal cancers revealed that PyNPase was as high as 70.2 +/- 18.5 unit/mg protein in the stroma fraction (SF), whereas it was 45.1 +/- 10.5 in the cancer fraction (CF) (p < 0.0001). Vessel density was correlated with PyNPase in the SF but not in the CF. In stage IIIb, 11 cases expressing a high level of PyNPase in the CF showed poorer prognosis than 10 cases with low-level PyNPase expression (p < 0.05), although the level of PyNPase expression in the SF did not affected the patients prognosis. Immunohistochemical examination indicated that PyNPase in the SF was mainly produced by macrophages (M phi), and therefore we investigated the profile of PyNPase production by M phi. In in vitro experiments PyNPase production by M phi was greatly enhanced by stimulation with OK-432, and the culture supernatant had the ability to convert 5'DFUR to 5-FU.

Antineoplastic Agents↗

Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia.

The improved outcome of acquired aplastic anemia (AA) has revealed later complications, such as myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). We retrospectively analyzed 167 children with severe acquired AA. Eleven of 50 children treated with cyclosporin (CSA) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) developed MDS/AML; 8 of these were within 36 months of the diagnosis of AA, much earlier than previous reports. Six of the 11 children received rhG-CSF exceeding 10 microg/kg/d, and 9 received rhG-CSF therapy for over 1 year. Ten children showed monosomy 7 at diagnosis of MDS. All of the 11 children were administered both CSA and rhG-CSF. There was no development of MDS/AML among 41 children treated with either CSA or rhG-CSF or among 48 children who underwent bone marrow transplantation. A well-controlled clinical trial is warranted to determine whether therapeutic modalities affect the development of MDS/AML in children with severe acquired AA.

Acute Disease↗

T-stem cell leukemia/lymphoma with both myeloid lineage conversion and T-specific delta recombination.

We evaluated retrospectively the clinical and biological characteristics of six patients with CD7+ early T-acute lymphoblastic leukemia and lymphoma (T-ALL/LBL) originating from prothymocyte stage I (pro-T I) or II cells. Patients exhibited mediastinal mass (five of six) and lymphoadenopathy (five of six) but without leukocytosis and circulating blast cells (six of six). All patients achieved a complete remission. All but one had a relapse with a transformation to the mixed type (triphenotype--three cases, biphenotype-two cases) including myeloid features in three patients. The altered phenotypes were myeloperoxidase (MPO)+ (three of five), CD13+ (four of five), CD33+ (three of five) and CD19+ (three of five). The difference for MPO-positivity were observed between the bone marrow (BM)- and lymph node (LN)-blast cells (three of three). On cytogenetic analysis, there is no common abnormality in these patients. Immunomolecular analysis revealed T-cell lineage specific delta gene rearrangements [D delta 2-J delta 1 (five of six) and V delta 1-J delta 1 (one of six)] in all cases. Furthermore, D delta 2-J delta 1 occurred even in the cases with the pro-T I phenotype. Rearrangements of TCR beta, gamma or immunoglobulin heavy chain genes occurred in three patients. The same rearranged band(s) appeared at both diagnosis and relapse, indicating the same originality of the pro-T leukemic cell clone (three of three). We suggest that this type of CD7+ early T-ALL/LBL was transformed from a pro-T I or II cell, such as T-stem cell leukemia/lymphoma, which is a subtype of CD7+ stem cell leukemia as defined by Kurtzberg et al. This study reveals that pro-T I and II cells might be capable of myeloid, T- and B-lymphoid differentiation, and T-cell lineage specific TCR delta recombination occurs.

Adult↗

Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children.

Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m2), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m2). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n = 1), interstitial pneumonitis (n = 1) and veno-occlusive disease of the liver (n = 1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69 +/- 15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well.

Antineoplastic Combined Chemotherapy Protocols↗

Acute hepatic failure following transcatheter arterial embolization for the treatment of hepatocellular carcinoma.

We conducted a retrospective analysis to evaluate the risk factors associated with the occurrence of acute hepatic failure following transcatheter arterial embolization (TAE) for hepatocellular carcinoma. From 1984 to 1993 we performed a total of 623 embolization procedures in 369 patients with both hepatocellular carcinoma and chronic liver disease. Within 2 weeks after TAE, 13 patients (2.1%) experienced hepatic failure as characterized by a rapid increase in serum bilirubin levels and the development of hepatic encephalopathy of grade 2 or higher. These results indicated that the following are risk factors for acute hepatic failure after TAE: poor hepatic functional reserve; high-dose infusion of chemotherapeutic agents, and a history of multiple embolization procedures.

Acute Kidney Injury↗

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Adult↗

Antitumor effect of transcatheter oily chemoembolization for hepatocellular carcinoma assessed by computed tomography: role of iodized oil.

The efficacy of transcatheter oily chemoembolization (TOCE) was evaluated in 82 patients with unresectable hepatocellular carcinoma (HCC) by computed tomography more than 6 months after TOCE. A doxorubicin in oil emulsion (DOE) was administered to 42 cases and an epirubicin in oil emulsion (EOE) was administered to 40 cases. No significant differences were found in the patient background characteristics between the DOE-treated group and the EOE-treated group. Tumor regression of more than 50% of the product of two dimensions was observed in 26 DOE-treated cases and in 25 EOE-treated cases at 1 year or more after TOCE. No difference in antitumor effect was observed between DOE and EOE, although a sufficient dose per tumor volume would be required to manifest an antitumor effect on hepatocellular carcinoma.

Antibiotics, Antineoplastic↗

Appraisal of combination treatment for hepatocellular carcinoma: long-term follow-up and lipiodol-percutaneous ethanol injection therapy.

Since 1988, 124 patients with hepatocellular carcinoma were treated in our departments. Among them, 31 cases treated by surgical resection and 30 cases administered a combination therapy (Lipiodol [Laboratoire Guerbet, Villepinte, France]-transcatheter arterial embolization [L-TAE] and lipiodol-percutaneous ethanol injection therapy [L-PEIT]) were analyzed retrospectively. The 1-, 3-, and 5-year survival rates were, respectively, 89.0%, 72.7%, and 63.6% for the surgical resection group and 93.3%, 72.8%, and 42.0% for the combination therapy group. The follow-up results at less than 4 years after the procedures revealed that the survival rate with the combination therapy was slightly better than that with the surgical treatment. However, in the subsequent 4 years, the survival rate of the combination therapy group decreased rapidly. The reasons for this deterioration were local recurrence and/or new primary lesions of hepatocellular carcinoma, mainly due to inappropriate ethanol injection. To achieve adequate and accurate injection of ethanol, a 10% volume of Lipiodol was mixed with the ethanol so that the location of the injected ethanol could be easily confirmed. The effectiveness of L-PEIT was thus confirmed by computed tomography, performed on the following day. Defective Lipiodol accumulation in the tumor and/ or neighboring tissues was able to be corrected by additional ethanol injections. With this L-PEIT technique, the tumor necrosis rate is now improving. Therefore, a better prognosis is expected.

Antibiotics, Antineoplastic↗

Treatment of high-risk acute lymphoblastic leukemia in children using the AL851 and ALHR88 protocols: a report from the Kyushu-Yamaguchi Children's Cancer Study Group in Japan.

A total of 125 children, who were diagnosed as having high-risk acute lymphoblastic leukemia (ALL), were treated with two consecutive protocols designated as AL851 (1985-1988) and ALHR88 (1988-1990). All patients received induction therapy consisting of vincristine (VCR), prednisolone (PSL), daunorubicin (DNR), and I-asparaginase (I-Asp). In the ALHR88 protocol, the patients whose blasts in the bone marrow (BM) were > or = 25% on day 14 of induction therapy and who were classified into T-cell type received additional cytosine arabinoside (AraC). After consolidation with intermediate-dose methotrexate (MTX), reinduction therapy including VCR, dexamethasone, and adriamycin followed by high-dose AraC was done for all patients. Intrathecal MTX and 24Gy of cranial irradiation were used to prevent central nervous system leukemia. A maintenance therapy consisting of 6-mercaptopurine, cyclophosphamide, MTX, DNR, VCR, and AraC was administered for 3 years after achieving a complete remission (CR). CR was achieved in 51/55 (92.7%) for AL851 and 68/70 (97.1%) for ALHR88. The 5-year event-free survival rates were 49.1 +/- 6.7% in AL851 and 62.5 +/- 6.1% in ALHR88. The factors related to a poor prognosis were a high initial leukocyte count of greater than 50 x 10(9)/L (P < 0.001), an L2 morphology of leukemic cells by FAB classification (P = 0.009), the chromosomal abnormality (P = 0.004) and high residual leukemic cells in BM (> or = 25%) on day 14 of induction therapy (P < 0.001). Taking these factors into consideration, more intensive protocols were started in 1990 for the patients with high-risk ALL.

Adolescent↗

Childhood acute lymphoblastic leukemia relapse in the uterine cervix.

PURPOSE: Extramedullary relapse outside the testes and CNS is rare in children with acute lymphoblastic leukemia (ALL). We describe a case of a recurrence of ALL in the uterine cervix during hematopoietic remission. RESULTS: Primary recurrence in the uterine cervix was diagnosed by cytology with immunochemistry 43 months after initial diagnosis. She was successfully treated with systemic chemotherapy, without hysterectomy or irradiation. She remains in second complete remission 54 months after relapse. CONCLUSIONS: Immunocytochemistry using monoclonal antibodies against cell surface antigens made the cytologic diagnosis of leukemic relapse in the uterine cervix possible. Systemic chemotherapy is the first treatment of choice for ALL recurrence in the genital tract in a patient without poor prognostic factors in order to spare gonadal function and reproductive potential.

Antigens, CD↗

Acute leukemias expressing p210-and p 190-type bcr/abl mRNAs: report of two cases and review of the literature.

We report two patients with acute leukemias who expressed two types of bcr/abl mRNA. The first case was an 8-year-old boy with acute mixed leukemia in whom the Ph1 chromosome and p210/p190 types of bcr/abl mRNAs were detected at diagnosis. The second case was a 39-year-old male with acute nonlymphocytic leukemia transformed from myelodysplastic syndrome (refractory anemia with excess of blasts). In the latter case, the p210-type mRNA appeared after leukemic transformation, and the p190-type transcript was detected only during the late stage when the Ph1 chromosome was first observed. The leukemias in these two patients were aggressive in their clinical courses. We conclude that the dual expression of p210 and p190 types of bcr/abl is a factor indicating a poor prognosis, and that, in some patients, p190-type bcr/abl may contribute to disease progression.

Acute Disease↗

Clinical and prognostic implications of bone lesions in childhood leukemia at diagnosis.

We studied 168 children with acute lymphoblastic leukemia (ALL) and 57 with acute nonlymphoblastic leukemia (ANLL) by retrospectively analyzing clinical symptoms, bone or joint involvement, and hematological findings to verify the clinical features and prognosis of children with acute leukemia who showed radiographic bone changes at the time of diagnosis. Of these, 36 with ALL (21.4%) and 6 with ANLL (10.5%) had symptoms referable to the bones or joints. Thirteen patients (7.7%) with ALL showed bone lesions radiographically. Phenotypically, 12 of the 13 had common ALL, 8 were incorrectly diagnosed and had received treatment for osteomyelitis or juvenile rheumatoid arthritis for 1 to 7 months prior to diagnosis of ALL. Leukocyte count was nearly normal with few or no blasts, and anemia and thrombocytopenia were mild or absent in all patients. Twelve of them remained in a complete remission for 26 to 148 months. Our data suggest that children with bone lesions related to acute leukemia exhibit clinical features that mimic infectious or collagen disease at diagnosis, and may belong to a subgroup of ALL with a better prognosis.

Adolescent↗

High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia.

We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.

Antigens, CD↗

[Intra-arterial infusion chemotherapy for liver metastases from breast cancer].

Twelve patients with liver metastases of breast cancer were treated with hepatic arterial infusion chemotherapy using 20-30 mg/body of epi-adriamycin (epi-ADM) every 2 weeks and continuous infusion of 250 mg/body/day of 5-fluorouracil (5-FU). All patients were followed by systemic chemo-endocrine therapy with oral administration of 600-1,200 mg/day of me droxyprogesterone acetate (MPA) alone or with 600-800 mg/day of 5'-deoxy-5-flurouridine (5'-DFUR). The response rate was 41.7% (5/12 cases). Duration of response was 2-28 months (mean 10 months). At one year, the survival rate was 46.8% (Kaplan-Meier method). As for side effects, gastrointestinal disturbance, bone marrow depression and alopecia were mild. These results suggest that hepatic arterial infusion therapy in combination with MPA is safe and effective for controlling liver metastases of breast cancer.

Adult↗

[Effect of FUT-187, oral serine protease inhibitor, on inflammation in the gastric remnant].

Excessive enterogastric reflux following partial gastrectomy is believed to be responsible for the cause of inflammation in the gastric remnant. We examined the effect of FUT-187, a synthetic serine protease inhibitor, on symptoms and endoscopic findings in 33 patients who were diagnosed endoscopically as postgastrectomy gastritis. Patients took 50 mg FUT-187 orally after each meal and at bedtime for 8 weeks. Before treatment, 30 patients (91%) suffered from several symptoms including regurgitation and/or bitter taste in the mouth (49%), epigastric pain (42%) and nausea (36%). From endoscopic observation, erythema was detected in 32 patients, edema in 23 patients and erosion and/or ulcer in 9 patients. After treatment the global improvement rating for subjective symptoms was 76.7% (23/30) and the improvement of endoscopic findings was 63.6% (21/33). Diarrhea was observed in one patient but could be easily controlled by discontinuation of the drug. Our results suggest that FUT-187 can be a useful drug for the treatment of postgastrectomy gastritis with its efficacy and safety.

Administration, Oral↗

Occurrence of acute megakaryoblastic leukemia in a patient with idiopathic growth hormone deficiency.

We describe a case of a 15 year old boy who developed acute megakaryoblastic leukemia (AMKL) while receiving treatment with human growth hormone (hGH) for idiopathic growth hormone deficiency (GHD). He was diagnosed as having idiopathic GHD and given hGH from December 1991. The examination of his peripheral blood showed mild pancytopenia 2 months before the start of the hGH therapy. Since January 1992, paleness of the skin, general fatigue and fervescence progressed gradually. In February 1992, because of the occurrence of acute leukemia, administration of hGH was discontinued. Judging from the results of surface marker analysis of the blast cells, the patient was diagnosed as having AMKL. He was treated with chemotherapy for acute non-lymphoblastic leukemia from March 1992. A complete remission was obtained after 4 weeks of treatment. The chemotherapy was completed in July 1993. He remains in complete remission 26 months after diagnosis. This case suggests the importance of hematological examination and, when there is any abnormality which is not caused by GHD, such as pancytopenia, more detailed medical examinations (for example bone marrow examination) are necessary.

Child↗