T Yano

Okayama University, Okayama, Okayama, Japan

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Publications (21)86.84 Total impact

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    ABSTRACT: We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in Japan. A propensity score method was used to compensate for the non-randomized study design. From January 2000 to December 2004, 378 patients who were newly diagnosed with DLBCL at 13 institutes were enrolled: 123 in the rituximab plus CHOP-based chemotherapy (R+) group, and 255 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (77.7 vs. 69.4%, P < 0.001). The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 70.5% for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43-0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited younger patients (hazard ratio 0.25, 95% CI 0.08-0.75, P = 0.013). IPI also showed significant impact for PFS (hazard ratio 1.82, 95% CI 1.55-2.14 for one score increase, P < 0.001) as well as OS (hazard ratio 2.10, 95% CI 1.71-2.57, P < 0.001). In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for Japanese DLBCL patients, particularly younger patients.
    International journal of hematology 05/2009; 89(3):326-31. · 1.17 Impact Factor
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    ABSTRACT: A prospective randomized clinical trial assessed the efficacy and tolerance of micafungin compared with that of standard fluconazole treatment in patients undergoing hematopoietic stem cell transplantation (HSCT). Adult patients (n = 106) were randomly assigned to receive prophylaxis with either micafungin 150 mg (n = 52), or fluconazole 400 mg (n = 52). Success was defined as the absence of suspected, proven, or probable invasive fungal infection (IFI) through the end of therapy and the absence of proven or probable IFI through the end of the 4-week period following treatment. The overall efficacy of micafungin was comparable to that of fluconazole (94 vs. 88%; difference 6.0%; 95% confidence interval, -5.4 to +17.4%; P = 0.295). A total of 2 (4.0%) of 50 patients in the micafungin arm and 6 (12.0%) of 50 patients in the fluconazole arm received empirical antifungal therapy (P = 0.06). Micafungin treatment did not result in increasing adverse effects and had a safe profile as fluconazole in neutropenic patients. This randomized trial indicates that the efficacy and tolerance of micafungin 150 mg was comparable to that of fluconazole 400 mg, suggesting that micafungin at 150 mg daily represents a valuable new treatment option for antifungal prophylaxis in HSCT recipients.
    International journal of hematology 12/2008; 88(5):588-95. · 1.17 Impact Factor
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    ABSTRACT: Clinical effects and safety of cefozopran (CZOP) were evaluated by the Okayama Bone Marrow Transplantation Group. Twenty-five patients expected to experience febrile neutropenia during induction chemotherapy or consolidation chemotherapy of acute leukemia were enrolled between July 2000 and November 2002. CZOP was administrated by drip infusion at 4g/day bid for a minimum of 3 days. The clinical effects and safety were evaluated in 20 patients with fever of 37.5 degrees C or more from a clinically suspected infection. The underlying disease was acute myeloid leukemia in 17 patients, acute lymphoid leukemia in 1 and acute promyelogeneous leukemia in 1. The complicating infections were sepsis and suspected sepsis. Clinical efficacy was excellent in 11 patients, good in 1, fair in 2 and poor in 6, with an efficacy rate of 60.0%. The efficacy rate in patients whose albumin levels before therapy were less than 3.8 g/dl was 37.5%, whereas the rate in patients whose albumin levels before therapy were between 3.8 g/dl and 5.3 g/dl was 80.0%. The efficacy rate in patients whose neutrophil counts before therapy were less than 100/microliter was 50.0%, whereas the rate in patients whose neutrophil counts after therapy were less than 100/microliter was 53.8%. The efficacy rate in patients whose neutrophil counts both before and after therapy were less than 100/microliter was 37.5%. Side effect of exanthema was observed in 1 patient. These results indicate that CZOP is an effective and safe antibiotic for the treatment of febrile neutropenia in patients with hematological malignancies.
    Gan to kagaku ryoho. Cancer & chemotherapy 02/2004; 31(1):61-5.
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    ABSTRACT: In two-thirds of patients with splenic lymphoma with villous lymphocytes (SLVL) a small amount of M-protein can be detected in association with the presence of plasma cells in the peripheral blood (PB) and/or bone marrow (BM). However, it is not known whether lymphoma cells and plasma cells originate from the same clone. In this report we describe a case of SLVL which was characterized by the presence of marked monoclonal gammopathy (IgG-κ 90 g/l) and increased plasma cells in the BM. In an attempt to elucidate the origin of lymphoma cells and plasma cells, we performed morphological, cytogenetic and molecular studies on PB mononuclear cells (PBMNC) without plasma cells and BMMNC containing 10% plasma cells from this patient.Immunofluorescence showed that lymphoma cells and plasma cells were positive for cytoplasmic γ heavy and κ light chains. Well-developed endoplasmic reticulum was observed in the cytoplasmic organelles of PBMNC using an electron microscope. The mean IgG concentration in the 3 d supernatant cultures of PBMNC was 374±24μg/l. More than 50% PBMNC differentiated into plasmacytoid cells in 6 d of liquid culture with IL-3 and IL-6. Analysis by two-colour FISH revealed that karyotypic abnormalities of monosomy X and trisomy 17 existed simultaneously in both lymphoma cells and plasma cells. JH gene rearranged bands from PBMNC and BMMNC by Southern blot hybridization were identical, whereas DNAs from PBMNC failed to hybridize with the Cμ probe.These observations strongly suggest that lymphoma cells and plasma cells originate from the same clone, and that plasma cells, as well as lymphoma cells, which have undergone class switch recombination, could produce IgG type M-protein in this case.
    British Journal of Haematology 10/2003; 97(3):626 - 634. · 4.94 Impact Factor
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    ABSTRACT: We report a case of therapy-related myelodysplastic syndrome (t-MDS) with t(10;16)(q22;p13), in which novel fusion transcripts of the MORF and CBP genes were detected. In one MORF-CBP fusion transcript, exon 15 of the MORF gene was fused in frame with exon 5 of the CBP gene. In a reciprocal CBP-MORF transcript, exon 4 of the CBP gene was fused in frame with exon 16 of the MORF gene. This is the first reported case of t-MDS associated with t(10;16), and provides molecular evidence that the novel MORF-CBP and/or CBP-MORF fusion protein(s) might play an important role in the development of t-MDS.
    British Journal of Haematology 02/2003; 120(2):271-3. · 4.94 Impact Factor
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    ABSTRACT: Gene targeting studies in mice have shown that the transcription factor Ikaros plays an essential role in lymphoid development and as a tumor suppressor in T cells, whereas the related gene Aiolos functions as a tumor suppressor in B cells. We analyzed the expression levels of the Ikaros gene family, Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5)]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting. None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis. Southern blotting analysis with PstI digestion revealed that those patients with the dominant negative isoform Ik-6 might have small mutations in the Ikaros locus. We did not detect any overexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell malignancies through the dominant negative isoform Ik-6.
    Cancer Research 09/2000; 60(15):4062-5. · 8.65 Impact Factor
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    ABSTRACT: Although the use of allogeneic transplants of peripheral blood stem/progenitor cells (PBSCs) is increasing, the precise mechanism of PBSC mobilization has not yet been fully clarified. We examined the expression of some adhesion molecules on CD34+ cells from steady-state bone marrow (BM), granulocyte colony-stimulating factor (G-CSF)-mobilized PBSCs, and cytotoxic drugs plus G-CSF-mobilized PBSCs. Irrespective of mobilization method, very late antigen (VLA)-4 expression on circulating CD34+ cells was significantly lower than on steady-state BM CD34+ cells. To elucidate the influence of lineage commitment on VLA-4 expression of circulating CD34+ cells, we analyzed VLA-4 expression on different subsets of CD34+ cells with or without CD33, CD38, CD5, or CD10 antigens, or Glycophorin A in G-CSF-mobilized PBSCs and steady-state BM from related donors, using 3-color flow cytometry. VLA-4 on circulating CD34+ subsets was less expressed than on each corresponding subset of steady-state BM CD34+ cells. Furthermore, VLA-4 positive rates showed no significant difference among the CD34+ subsets. Finally, the data comparing CD34+ cells from steady-state and G-CSF-mobilized PBSCs revealed no differences in terms of VLA-4 expression. These data suggest that reduced expression of VLA-4 may be a result of peripheralization of CD34+ cells from bone marrow, which occurs in a G-CSF- and lineage-independent fashion.
    International Journal of Hematology 07/2000; 71(4):328-33. · 1.68 Impact Factor
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    ABSTRACT: Despite a 10-fold increase of T cell dose, the incidence and severity of acute GVHD following allogeneic transplantation of G-CSF-mobilized PBSC is not increased compared to BMT. Experimental murine studies demonstrate that G-CSF polarizes donor T cells toward a type 2 cytokine response. To determine whether G-CSF alters T cell cytokine responses, we investigated the effects of G-CSF administration on T cell proliferative and cytokine responses to alloantigen and Con A in nonadherent PBMC (NAC) and CD3+ T cells obtained from normal individuals before and after G-CSF administration (10 μg/kg × 4 days). Although T cell proliferative and cytokine (IFN-γ and IL-4) responses to alloantigen stimulation and Con A were significantly reduced in post-G-CSF NAC, they were restored by the removal of non-T cells from post-G-CSF NAC. Furthermore, there was less T cell alloreactivity in MLR in the presence of autologous post-G-CSF monocytes than in the presence of pre-G-CSF monocytes. This alteration was not replicated in vitro by culturing PBMC with G-CSF. These results suggest that G-CSF administration suppresses T cell proliferative and cytokine (IFN-γ and IL-4) responses to allogeneic stimulation by indirectly modulating monocyte function. Bone Marrow Transplantation (2000) 25, 1035–1040.
    Bone Marrow Transplantation 01/2000; 25(10):1035-1040. · 3.54 Impact Factor
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    ABSTRACT: T-cell prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell neoplasm which shares most clinical features with adult T-cell leukemia (ATL). We measured serum level of C-terminal parathyroid hormone-related protein (C-PTHrP) in patients with T-PLL and ATL. Serum C-PTHrP levels of eight patients with T-PLL (median 36.8 pmol/l; range 27.0-50.2 pmol/l) did not differ from those of 30 human T-lymphotropic virus type I (HTLV-I)-seronegative blood donors (median 37.0 pmol/l; range 22.6-54.0 pmol/l). The C-PTHrP levels in ten ATL patients (median 69.6 pmol/l; range 42.5-899.4 pmol/l) were significantly higher than those in healthy controls (p<0.0001) or T-PLL patients (p=0.001). We suggest that the serum level of PTHrP can provide useful information for differentiating between T-PLL and ATL.
    Annals of Hematology 10/1999; 78(9):415-7. · 2.87 Impact Factor
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    ABSTRACT: T-cell prolymphocytic leukaemia (T-PLL) is a rare form of post-thymic T-cell neoplasm, the aetiology of which remains unknown. We examined human T-lymphotropic virus (HTLV) provirus in five HTLV-I/II seronegative patients with T-PLL. Southern blotting did not show monoclonal integration of the HTLV-I genome in any of the DNA samples. However, two of the five DNA samples contained an HTLV-I tax sequence. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and LTR regions were all negative. HTLV-I tax gene expression and p40tax antibody were not detected in samples from cases with HTLV-I tax sequence. Our findings suggest that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis, in which HTLV-I genome insertion triggers T-PLL but the deletion of various regions of the integrated provirus subsequently prevents active replication and the expression of the virus.
    British Journal of Haematology 06/1999; 105(2):376-81. · 4.94 Impact Factor
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    ABSTRACT: Despite the therapeutic efficacy of allogeneic bone marrow transplantation (allo-BMT), circulating hematopoietic progenitor cells after bone marrow transplantation have not been well characterized. In the present study, we focused on these 'post-transplant circulating progenitor cells (PTCPC)' which may be on their way to bone marrow. We analyzed the number of myeloid progenitor cells (CFU-GM) per 10 ml of peripheral blood (PB) on days 0 (just before transplantation), 1 (8-15 h after the completion of transplantation), 2, 3, 5, 7, 10, 14, 17, 21, 28 and 35 after allo-BMT in five transplant patients using a standard methylcellulose assay. In addition, high proliferative potential colony-forming cells (HPP-CFC) of the harvested donor bone marrow (BM) and day 1 PB of recipients were assayed in five patients. The origin of HPP-CFC from day 1 PB was analyzed by polymerase chain reaction of a DNA region containing a variable number of tandem repeats. The replating potential of these HPP-CFC was evaluated by a secondary colony assay. The proportion of CD38negative cells among CD34+ cells in the harvested BM and day 1 PB was evaluated by two-color flow cytometric analysis. The number of CFU-GM on day 1 ranged from 6 to 73/10 ml PB, and became undetectable on day 5. The reappearance of PTCPC was observed on day 14, along with hematopoietic recovery. The proportion of HPP-CFC among myeloid colonies from day 1 PB was significantly higher than that from harvested BM (44.3+/-10.4% vs 11.3+/-2.1%, respectively, n=5, P=0.0030). These HPP-CFC from day 1 PB were confirmed to be of donor origin. More than 90% of these HPP-CFC had replating potential. Two-color flow cytometric analysis revealed that the proportion of CD34+CD38negative cells was significantly higher in day 1 PB than in the harvested BM (61.0+/-16.5% vs 9.3+/-3.5%, respectively, n=7, P=0.0002). These observations suggest that both primitive and committed transplanted myeloid progenitor cells may circulate in the very early period following allo-BMT.
    Bone Marrow Transplantation 05/1999; 23(7):659-65. · 3.54 Impact Factor
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    ABSTRACT: All-trans retinoic acid (ATRA), a potent differentiating drug for acute promyelocytic leukemia (APL), induces a high incidence of complete remission (CR) in patients with APL and is now established as a first-line therapy. However, ATRA resistance has become a clinical problem. Patients who relapsed after ATRA-induced CR have had difficulty in obtaining a second CR with ATRA therapy. Although several mechanisms have been postulated, treatment strategies to overcome resistance have not been established. We used a new synthetic retinoid, Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80 was several times more potent than ATRA in inducing differentiation in vitro. At a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro response to Am-80. Adverse effects included retinoic acid syndrome (n = 1), hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8), hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active in APL after relapse from ATRA-induced CR. Further clinical trials are needed to establish strategies to overcome ATRA resistance.
    Leukemia and Lymphoma 12/1998; 31(5-6):441-51. · 2.61 Impact Factor
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    ABSTRACT: We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.
    International Journal of Hematology 11/1998; 68(3):291-6. · 1.68 Impact Factor
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    ABSTRACT: We conducted a comparative study on a daily single versus a divided dose of G-CSF for G-CSF-induced mobilization of peripheral blood stem cells (PBSC) in eleven HLA-identical sibling donors of allogeneic PBSC transplantation (PBSCT). Six donors received double subcutaneous injections of G-CSF at a dose of 5 micrograms/kg x 2/day for 5 days (Group A), while the remaining five received single subcutaneous injection at a dose of 10 micrograms/kg/day for 5 days (Group B). The numbers of circulating CD34+ cells, myeloid progenitors (CFU-GM) and erythroid progenitors (BFU-E) reached peak values at day 5 of G-CSF administration in both groups. The mean number of CD34+ cells harvested per apheresis was 4.4 x 10(6)/kg (cells/body weight of each donor, range: 0.8-7.9 x 10(6)/kg) in Group A and 5.1 x 10(6)/kg (range: 3.0-9.0 x 10(6)/kg) in Group B. There were no significant differences between these two groups in total numbers of CFU-GM, BFU-E, or T-lymphocytes harvested. Adverse effects including mild to moderate bone pain and thrombocytopenia were transient and well tolerated. No difference was observed in the incidence of adverse effects between the two groups. These observations suggest that there is no difference in G-CSF-induced mobilization of PBSC between daily single and divided dose of G-CSF to collect a sufficient number of PBSC for engraftment after allo-PBSCT.
    International Journal of Hematology 09/1997; 66(2):169-78. · 1.68 Impact Factor
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    Blood 09/1997; 90(4):1716-8. · 9.06 Impact Factor
  • Blood 09/1997; 90(4):1716b-1718. · 9.06 Impact Factor
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    ABSTRACT: In two-thirds of patients with splenic lymphoma with villous lymphocytes (SLVL) a small amount of M-protein can be detected in association with the presence of plasma cells in the peripheral blood (PB) and/or bone marrow (BM). However, it is not known whether lymphoma cells and plasma cells originate from the same clone. In this report we describe a case of SLVL which was characterized by the presence of marked monoclonal gammopathy (IgG-kappa 90 g/l) and increased plasma cells in the BM. In an attempt to elucidate the origin of lymphoma cells and plasma cells, we performed morphological, cytogenetic and molecular studies on PB mononuclear cells (PBMNC) without plasma cells and BMMNC containing 10% plasma cells from this patient. Immunofluorescence showed that lymphoma cells and plasma cells were positive for cytoplasmic gamma heavy and kappa light chains. Well-developed endoplasmic reticulum was observed in the cytoplasmic organelles of PBMNC using an electron microscope. The mean IgG concentration in the 3 d supernatant cultures of PBMNC was 374 +/- 24 microg/l. More than 50% PBMNC differentiated into plasmacytoid cells in 6 d of liquid culture with IL-3 and IL-6. Analysis by two-colour FISH revealed that karyotypic abnormalities of monosomy X and trisomy 17 existed simultaneously in both lymphoma cells and plasma cells. JH gene rearranged bands from PBMNC and BMMNC by Southern blot hybridization were identical, whereas DNAs from PBMNC failed to hybridize with the Cmu probe. These observations strongly suggest that lymphoma cells and plasma cells originate from the same clone, and that plasma cells, as well as lymphoma cells, which have undergone class switch recombination, could produce IgG type M-protein in this case.
    British Journal of Haematology 07/1997; 97(3):626-34. · 4.94 Impact Factor
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    ABSTRACT: Two patients with relapsed acute promyelocytic leukaemia previously treated with all-trans retinoic acid (ATRA), were treated with a new synthetic retinoid, Am-80. In both patients pancytopenia gradually resolved without an increase in leukaemic cells, and differentiation of leukaemic cells was observed morphologically in bone marrow. Without the use of anti-leukaemic agents, both cases achieved complete remission (CR) on days 52 and 38 of treatment, respectively. On the day of CR, PML gene rearrangement and the t(15;17) translocation disappeared, though PML-RAR alpha chimaeric messenger RNA was still detected by reverse transcriptase polymerase chain reaction. Both patients then received conventional chemotherapy for consolidation of CR. These clinical experiences suggest that Am-80 may be an active agent for APL patients who have relapsed from ATRA-induced remission.
    British Journal of Haematology 05/1997; 97(1):137-40. · 4.94 Impact Factor
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    ABSTRACT: A simplified method for cryopreservation at -80 degrees C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplified method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37 degrees C. In our study, we found that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20 degrees C. These observations indicate that PBSC cryopreserved for at least 5 years by the simplified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic activity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when PBSC are thawed gradually at room temperature.
    Bone Marrow Transplantation 03/1997; 19(3):283-7. · 3.54 Impact Factor
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    ABSTRACT: We describe the spontaneous regression of a malignant pleural mesothelioma with left pleural effusion, chest pain, and a high fever (38° to 39°C) in a 37-year-old man. The patient was referred to us because multiple nodules were seen on his chest radiograph after he was successfully treated with thoracocentesis and conventional antibiotic therapy for pleural effusion. Our diagnosis was malignant pleural mesothelioma, based on histologic findings in a biopsy specimen obtained during thoracoscopy. Interestingly, the tumors markedly regressed without treatment, and the patient was doing well more than 5 months after the cancer was diagnosed. The spontaneous regression of malignant pleural mesothelioma is rare, and this may represent the first case report.
    International Journal of Clinical Oncology 01/1997; 2(2):118-120. · 1.73 Impact Factor

Publication Stats

231 Citations
86.84 Total Impact Points

Institutions

  • 2000–2009
    • Okayama University
      • Medical School
      Okayama, Okayama, Japan
  • 1999–2009
    • Okayama Rosai Hospital
      Okayama, Okayama, Japan
  • 1997
    • Minami Okayama Medical Center
      Okayama, Okayama, Japan