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Atsushi Makimoto

Publications and source records attributed to Atsushi Makimoto.

At least 19 recordsLinked to original sources
PubMed2006

Utility of immunohistochemical analysis for cyclo-oxygenase 2 in the differential diagnosis of osteoblastoma and osteosarcoma.

AIMS: To study the immunoexpression of cyclo-oxygenase (COX) 2 in osteoblastomas (OBs) and osteosarcomas (OSs), and to assess the utility of immunohistochemical analysis for COX 2 in the differential diagnosis of the two tumour forms. METHODS: The immunohistochemical features of COX 2 were studied in 11 OBs and 30 OSs, including 26 high-grade OSs (16 osteoblastic, 7 chondroblastic, and 3 fibroblastic) and 4 low-grade OSs. RESULTS: Tumour cells from all 11 OBs unequivocally showed diffuse, intense and cytoplasmic immunoreactivity for COX 2. Strong cytoplasmic expression of COX 2 was observed in 5 of 26 (19%) high-grade OSs, all chondroblastic. In one osteoblastic-type OS, COX 2 was expressed in the chondroblastic component, but this tumour was considered to be COX 2 negative. No COX 2 expression was noted in atypical osteoblastic cells. Staining in the four low-grade OSs was negative. CONCLUSION: The results of immunohistochemical analysis of COX 2 suggest that in addition to the routine histopathological evaluation, COX 2 is a valuable diagnostic marker in the distinction between OB and OS.

Adolescent↗
PubMed2006

Coincidental outbreak of methicillin-resistant Staphylococcus aureus in a hematopoietic stem cell transplantation unit.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens among hospital-acquired infections, and immunocompromised patients are highly susceptive to infection. The molecular typing of isolated strains is a common method for tracing an outbreak of MRSA, but experience with this approach is still limited in the hematopoietic stem cell transplantation (HSCT) ward. METHODS: We experienced 6 cases of MRSA infection/colonization in our 26-bed HSCT ward during a 4-week period. This unusual outbreak strongly suggested that the same MRSA strain was involved despite strict isolation and aseptic patient care. Clarification of the transmission pattern was critical, and we applied pulsed-field gel electrophoresis (PFGE) and amplified fragment length polymorphism (AFLP) assays for evaluation. RESULTS AND CONCLUSION: In four of the six cases, the pattern of bands examined by PFGE and AFLP analyses supported the idea that direct person-to-person transmission was very unlikely and the outbreak was coincidental. This experience highlights the clinical value of molecular typing methods for the clinical epidemiological assessment of MRSA outbreak.

Adult↗
PubMed2006

Nutritional support for patients suffering from intestinal graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Patients who exhibit gastrointestinal (GI) involvement due to graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) are often recommended to withhold oral intake (NPO) to avoid further damage to the GI mucosa. However, it is possible that continuing oral intake could be beneficial in many patients compared to total parenteral nutrition (TPN). OBJECTIVE: The primary objective of this prospective study was to evaluate whether programmed step-ladder oral dieting (enteral nutrition; EN) is feasible and beneficial for these patients. METHODS: A total of 18 patients who exhibited GI-acute GVHD (stage I to III gut GVHD) after SCT received an EN dieting program, and changes in clinical and laboratory parameters were compared to those in a control cohort of 17 patients who were placed on NPO with TPN. Patients with GVHD were included prospectively and those with intestinal bleeding/obstruction, severe pancreatitis, and cytomegalovirus enterocolitis were excluded. RESULTS: None of the patients in the EN group experienced significant adverse events, including exacerbation of GI symptoms. Although there was no statistically significant difference in the volume or frequency of diarrhea or the time to complete dietary recovery, parameters including body weight and serum levels of total protein and albumin tended to improve faster in the EN group. CONCLUSION: The EN diet is safely applicable to patients suffering from GI involvement by GVHD.

Adult↗
PubMed2006

Intensive multimodality therapy including paclitaxel and reduced-intensity allogeneic hematopoietic stem cell transplantation in the treatment of adrenal cancer with multiple metastases.

Adrenocortical carcinoma is a rare malignancy in adolescents and young adults. The prognosis of unresectable/metastatic adrenocortical carcinoma remains very poor because the rarity of the tumor has made it difficult to establish treatment guidelines, and diagnosis and the resultant treatment can be greatly delayed. We treated a 24-year-old woman who was diagnosed with adrenocortical carcinoma of the right adrenal gland which extended to the inferior vena cava. Although she underwent surgical resection of the extensive tumor as the primary treatment, the disease recurred in the lung and liver as multiple metastases shortly after surgery. She received intensive multimodality therapy, including chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen), embolization of the feeding arteries, and proton irradiation for the liver mass. Finally, she underwent reduced-intensity allogeneic hematopoietic stem cell transplantation from an HLA 1-locus-mismatched sibling donor. A prolonged survival of 39 months after the onset of the disease was achieved. Although this experience is limited, we suggest that TIP chemotherapy was effective for adrenocortical carcinoma, and a graft-versus-tumor effect after reduced-intensity stem cell transplantation may have contributed to the prolonged survival.

Adrenal Gland Neoplasms↗
PubMed2005

Expression of epidermal growth factor receptor, ERBB2 and KIT in adult soft tissue sarcomas: a clinicopathologic study of 281 cases.

BACKGROUND: Little is known about the expression of receptor tyrosine kinases in adult soft tissue sarcomas (STS). In the current study, the authors analyzed the expression of epidermal growth factor receptor (EGFR), ERBB2, and KIT in 281 patients with STS who were treated in a single institution. Verification of the presence of an association with prognosis was performed. METHODS: The current study included 281 adult patients with STS of the extremity and trunk who were diagnosed and treated in the National Cancer Center, Tokyo. Expression was assessed using immunohistochemical stains for EGFR, ERBB2, and KIT on formalin-fixed, paraffin-embedded tissue sections by standard avidin-biotin peroxidase complex technique and EGFR detection system. RESULTS: Positive staining of EGFR was observed in 168 of 281 (60%) patients. Positive staining was common in pleomorphic malignant fibrous histiocytomas (89%), myxofibrosarcomas (89%), synovial sarcomas (76%), malignant peripheral nerve sheath tumors (89%), and leiomyosarcomas (73%). It was less common in well differentiated liposarcomas (38%), fibrosarcomas (36%), and myxoid liposarcomas (6%). In contrast, positive staining of ERBB2 and KIT was very limited. Increased levels of EGFR were significantly associated with a decreased probability of overall survival (P = 0.01), although by univariate analysis; probability of overall survival at 5 years was 64% in patients with increased levels of EGFR and 79% in patients without such overexpression. The overexpression of EGFR was significantly associated with histologic grade (P < 0.001). Moreover, stratified log-rank test revealed that there is an interrelation between EGFR overexpression and histologic grade. CONCLUSIONS: EGFR overexpression was found to be a negative prognostic factor of adult STS, which is strongly associated with histologic grade. STS patients with EGFR overexpression may benefit from treatment with currently available biospecific inhibitors for EGFR.

Adult↗
PubMed2005

A prospective trial to evaluate the safety and efficacy of pravastatin for the treatment of refractory chronic graft-versus-host disease.

This prospective study evaluates the safety and efficacy of pravastatin for the treatment of chronic graft-versus-host disease (GVHD). We included 18 patients with refractory chronic GVHD. Oral pravastatin was started at 10 mg/day, and the dose was increased up to 40 mg/day in 4 weeks. This maximum dose was administered over 8 weeks. There were no severe adverse events caused by pravastatin. A clinical response was observed in the skin score in two patients, mouth score in five patients, eye score in two patients, liver score in three patients, platelet count score in one patient, and weight loss in two patients. The overall response rate was 28%. Immunophenotypic analyses showed that T-helper (Th)1 cells were dominant in all but one patient before treatment and that the Th1/Th2 ratio tended to be lower in the responders than in the nonresponders. A randomized controlled trial is warranted to evaluate the efficacy of pravastatin against chronic GVHD.

Chronic Disease↗
PubMed2005

[Treatment for Ewing's sarcoma family of tumors in children].

The outcome of patients with Ewing Sarcoma Family of Tumors (ESFT) in our country is poor in comparison with American and European. We performed a review of the relevant data regarding the current status in the treatment of ESFT. The results of the major American and European cooperative groups were discussed, including the treatment strategies used and the prognostic factors identified for both localized and metastatic ESFT. We also discussed a new trial for the establishment of the standard treatment of ESFT in our country.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Results of treatment of retinoblastoma that has infiltrated the optic nerve, is recurrent, or has metastasized outside the eyeball.

Since the development of chemotherapy regimens for patients with retinoblastoma started in the 1950s, various agents and regimens have been employed for various kinds of patients. Chemotherapy has been employed for: (1) patients with high-risk features for metastases, such as patients with optic nerve involvement, (2) patients with orbital involvement, and (3) patients with distant metastasis. Effective systemic chemotherapeutic agents include vincristine, doxorubicin, cyclophosphamide, etoposide, cisplatin, and carboplatin, and, as well, intrathecal agents, including methotrexate, cytarabine, and corticosteroids are available. With the addition of appropriate chemotherapies to the conventional treatment modalities such as enucleation and radiotherapy, patients with advanced retinoblastoma are expected to obtain a survival benefit. Moreover, a new modality combined with autologous stem cell support allowed us to use high-dose alkylating agents such as thiotepa, melphalan, and cyclophosphamide, which resulted in better prognosis for patients with metastatic retinoblastoma. Because of the small number of patients with retinoblastoma and the diversity of the disease characteristics in individual patients, there have been no clinical trials to determine whether to recommend a particular regimen, or to identify specific criteria in patients who would benefit from chemotherapy. Well-designed prospective controlled trials are warranted to establish a standard treatment strategy for patients with extraocular retinoblastoma.

Drug Therapy↗
PubMed2004

Allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen for treatment of metastatic renal cell carcinoma: single institution experience with a minimum 1-year follow-up.

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of allogeneic hematopoietic stem cell transplantation with a reduced-intensity conditioning regimen (RIST) for interferon-alpha-refractory metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Of 26 patients referred to the National Cancer Center Hospital for possible RIST between June 2000 and April 2002, an HLA-identical relative was identified for 12 patients. Nine patients underwent RIST. The conditioning regimen consisted of fludarabine 180 mg/m2 or cladribine 0.66 mg/kg, plus busulfan 8 mg/kg and rabbit antithymocyte globulin 5 mg/kg. Graft-vs-host disease (GVHD) prophylaxis was cyclosporine alone. RESULTS: All patients achieved engraftment without grade III to IV nonhematologic regimen-related toxicity. All patients achieved complete donor-type chimerism without donor lymphocyte infusion by day 60. Four patients developed acute GVHD, and four developed chronic GVHD. One patient (11%) achieved partial response. As of July 2003, six patients were alive at median follow-up of 681 days. The actuarial overall survival rate was 89% at 1 year and 74% at 2 years. The overall survival rate tended to be higher in the 12 patients with a matched donor than in the other 14 patients without a matched donor (p = 0.088). CONCLUSION: Our RIST procedure is feasible without severe toxicity. The efficacy of RIST for RCC should be confirmed in phase II/III clinical trials.

Acute Disease↗
PubMed2004

Balance between acute graft-versus-host disease and graft-versus-tumor effect after reduced-intensity transplantation for metastatic renal cell carcinoma.

We describe a patient who had received reduced-intensity stem cell transplantation (RIST) for metastatic renal cell carcinoma (RCC). A 37-year-old man developed rapid progression of RCC during steroid therapy for immune-mediated thrombocytopenia and graft-versus-host disease (GVHD). After discontinuation of corticosteroid, RCC achieved long stable disease with the presence of chronic GVHD, despite low dose of prednisolone. This case suggests the impact of immunosuppression on progression of metastatic RCC after RIST.

Acute Disease↗
PubMed2004

Reduced-intensity hematopoietic stem cell transplantation (RIST) for solid malignancies.

Reduced intensity stem cell transplantation (RIST) is a new approach of stem cell transplantation, which has shown promising features as reported in multiple phase I and II studies. Elderly patients, who are not eligible for conventional myeloablative hematopoietic stem cell transplantation (HSCT), are now treatable with RIST. It has also reduced regimen-related toxicity and provided better prognosis in short-term follow-up than conventional HSCT. Among solid tumors, metastatic renal cell carcinoma was found to respond well to RIST. Clinical studies are currently being conducted to evaluate the efficacy of RIST in other types of solid tumors. However, the mechanism of graft-versus-host disease (GVHD) and graft-versus-tumor (GVT) effects remains unclear. More knowledge on the mechanism is crucial to enhance the antitumor effect and to improve the prognosis further.

Animals↗
PubMed2003

Cryopreservation of mobilized blood stem cells at a higher cell concentration without the use of a programmed freezer.

Cryopreservation of peripheral blood stem cells (PBSC) mobilized by chemotherapy combined with or without granulocyte colony-stimulating factor (G-CSF) is an essential part of procedure for anti-cancer strategies. We evaluated whether a higher cell concentration (2 x 10(8)/ml) without the use of a programmed freezer was acceptable for the storage of mobilized PBSC in an autologous setting. Mobilized PBSC were enriched to mononuclear cells (MNC) by Percoll separation and then frozen at cell concentrations of 2-5 x 10(7)/ml (group I, n=20) or 2 x 10(8)/ml (group II, n=44) without the use of a programmed freezer using 5% DMSO, 6% hydroxy ethyl starch, and 4% autologous serum or human albumin. CD34+ cells purified by ISOLEX300 were frozen at 2 x 10(7)/ml (group III, n=22) using the same method. The median recovery rates of CD34+ cells and CFU-GM were, respectively, n.d. (not determined) and 88% in group I, 103 and 64% in group II, and 98 and 53% in group III. There was a statistical significance between the recovery rate of CFU-GM in group III and that in group I ( p=0.02). The median percentage of cell viability after thawing in each group was 89, 87, and 75%, respectively. The median numbers of days after PBSCT to achieve a WBC of >1.0 x 10(9)/l, an absolute neutrophil count of >0.5 x 10(9)/l, and a platelet count of >50 x 10(9)/l were, respectively, 11, 11 and 15 in group I; 12, 12 and 16 in group II; and 12, 12 and 27 in group III. These results suggest that enriched MNC from mobilized PBSC could be frozen at a higher cell concentration (2 x 10(8)/ml) without the use of a programmed freezer, leading to reduction of the toxicities associated with infusion of thawed cells and of costly space required for cell storage.

Adolescent↗
PubMed2003

Antithymocyte globulin affects the occurrence of acute and chronic graft-versus-host disease after a reduced-intensity conditioning regimen by modulating mixed chimerism induction and immune reconstitution.

BACKGROUND: There have been no detailed analyses of the induction of donor cell-type chimerism, the onset and incidence of acute and chronic graft-versus-host disease (GVHD), and the immune recovery kinetics after reduced-intensity stem cell transplantation (RIST). METHODS: To address these, with particular emphasis on the impact of the use of antithymocyte globulin (ATG) in RIST, we compared 39 consecutively registered patients who underwent RIST from an HLA-matched related donor and 33 patients who underwent conventional marrow-ablative transplantation. RESULTS: The incidences of grades II to IV acute and chronic GVHD tended to be less in RIST with ATG than in either RIST without ATG or conventional marrow-ablative transplantation. In a multivariate analysis, the predictive factors for acute and chronic GVHD included, respectively, ATG and grades II to IV acute GVHD. In a chimerism analysis, the achievement of complete donor chimera in T-cell lineage was delayed in RIST without ATG compared with RIST with ATG (P=0.038), which might explain the observed delayed onset of acute GVHD in RIST with ATG compared with the other two regimens. The ratio of type 1 and 2 dendritic cells did not affect the development of GVHD, whereas the number of naive CD4+ T cells did. No difference was observed in the incidence of clinically definitive infection, including cytomegalovirus, among the three cohorts, regardless of the use of ATG. CONCLUSIONS: We suggest that the conditioning regimen and immunosuppressive strategy after RIST should be carefully balanced against the risk of GVHD and of relapse of the basic disorder caused by the lack of a graft-versus-leukemia benefit.

Acute Disease↗
PubMed2003

Impact of graft-versus-host disease in reduced-intensity stem cell transplantation (RIST) for patients with haematological malignancies.

To clarify the impact of graft-versus-host disease (GVHD) on the outcome of reduced-intensity stem cell transplantation (RIST), 40 patients who received RIST were compared with those who received conventional stem cell transplantation (CST). RIST regimens consisted of either cladribine (0.11 mg/kg/d x 6, n = 13) or fludarabine (30 mg/m(2)/d x 6, n = 27) with busulphan (BU, 4 mg/kg/d orally x 2), with or without antithymocyte globulin (ATG). CST regimens were either cyclophosphamide/total body irradiation (CY/TBI, n = 23), BU/CY (n = 19) or others (n = 6). The RIST group contained more patients who were at high risk of transplant-related mortality, including older patients, while the two groups contained the same percentages of patients at high risk of relapse. There were no differences between these groups in the incidences of acute (grade II-IV, 31.6% RIST vs 33.3% CST, P = 0.6742) and chronic GVHD (56.2%vs 64.1%, P = 0.8512), relapse rate (15.0%vs 18.8%, P = 0.6642), or overall (69.3%vs 65.6%, P = 0.4817) and progression-free survival (64.7%vs 63.8%, P = 0.6920) at d 500. Multivariate analysis of progression-free survival identified only grade III-IV acute GVHD and relapse risk dose as adverse risk factors. Although GVHD is a major threat in RIST, appropriate induction of GVHD may be associated with anti-tumour activity in RIST comparable to that of CST.

Acute Disease↗
PubMed2003

[Mini-transplantation for solid tumors].

With the hypothesis that RIST might be useful to induce immunological antitumor effect without excessive toxicities, we evaluated 27 patients(median age 38 years, range 4-59) with refractory non-renal solid tumors, who underwent RIST from the family donors. The primary and secondary endpoints included achievement of complete chimerism, and exploratory evaluation of graft-versus-tumor(GVT) effect, respectively. The conditioning regimen comprised purine analogue and busulfan with or without antithymocyte globulin. All patients achieved complete donor chimerism. These data demonstrate that RIST is a sufficient way to induce immune competent cells to patients with solid tumors. Although cases experienced probable GVT effect were observed in selective patients, total benefit for each tumor should be carefully evaluated in specific phase II-III trials.

Adolescent↗
PubMed2002

Limited efficacy of lamivudine against hepatitis B virus infection in allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Reactivation of chronic hepatitis B virus (HBV) infection is a major complication when HBV carriers receive immunosuppressive therapy. Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) carry the highest risk of fatal HBV disease (up to 12%). METHODS: In an attempt to identify a suitable procedure for the prevention and management of HBV reactivation, the administration of lamivudine over the course was tested in two patients. RESULTS: Generally, the patients transplant courses were successfully managed despite their difficult clinical situations: a high HBV load before transplant in one patient and intense steroid therapy for complicated acute graft-versus-host disease (GVHD) in the other patient. However, one patient showed a reactivation of HBV after discontinuing lamivudine and the other showed persistently high DNA polymerase activity despite prolonged administration of lamivudine. CONCLUSIONS: We concluded that lamivudine could have a place in the management of patients who suffer from chronic HBV infection and who are undergoing allogeneic HSCT. However, the efficacy of lamivudine seemed to be limited compared with other settings, including solid organ transplantation and autologous HSCT.

Adult↗
PubMed2002

Response-oriented preemptive therapy against cytomegalovirus disease with low-dose ganciclovir: a prospective evaluation.

BACKGROUND: Preemptive therapy against cytomegalovirus (CMV) disease has succeeded in reducing the incidence of CMV disease, but the toxicity of ganciclovir remains problematic. METHODS: We prospectively evaluated the efficacy and toxicity of a preemptive protocol with ganciclovir at a reduced initial dose in 40 patients who achieved engraftment after allogeneic hematopoietic stem cell transplantation. RESULTS: Twenty-three (58%) patients had high-risk features, including transplant from an HLA-mismatched or unrelated donor, or associated acute graft-versus-host disease. CMV antigenemia assay was performed weekly, and ganciclovir was started in a risk-adapted manner, in which the initial dose of ganciclovir was fixed at 5 mg/kg/d and then adjusted based on the results of a weekly CMV antigenemia assay. In this protocol, 23 (58%) patients demonstrated positive antigenemia, and 19 (48%) received a preemptive administration of ganciclovir. Only one patient had CMV disease in the gastrointestinal system, which was successfully treated with a regular therapeutic dose of ganciclovir. Consequently, the total dose of ganciclovir was significantly less than that in a previous protocol using the conventional double dose (5 mg/kg twice daily) of ganciclovir (134 mg/kg vs. 190 mg/kg on average, P=0.046). There were no significant toxicities attributed to ganciclovir, except for neutropenia <0.5 x 109/L, which developed in three patients for 3, 4, and 14 days, respectively, with granulocyte colony-stimulating factor support. CONCLUSION: Preemptive therapy with a low initial dose of ganciclovir appeared to be effective even in high-risk patients. Further randomized controlled trial is warranted.

Adult↗