Akitoshi Nagasaki

University of the Ryukyus, Okinawa, Okinawa, Japan

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Publications (64)180.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We report a rare case showing involvement with the cauda equina after autologous peripheral blood stem cell transplantation for primary plasma cell leukemia (PCL). A 55-year-old man was diagnosed with PCL(IgA-k type, stage III)in November of 2006. He was treated with VAD chemotherapy consisting of vincristine, doxorubicin, and dexamethasone. After achieving hematological remission, he received tandem high-dose melphalan supported by autologous peripheral blood stem cell transplantation. Five months after his second transplant, he complained of lumbago and bilateral leg pain. M-protein and Bence-Jones protein were not detected in serum or urine. An axial magnetic resonance imaging study revealed enlargement of the cauda equina nerve roots on T-1 weighted image. A sagittal T-1 weighted gadolinium-enhanced imaging study showed hyperintensities along the cauda equina. Leptomeningeal enhancement was also seen below the level of Th6. A cytological examination of the cerebrospinal fluid (CSF) with May-Giemsa stain showed atypical plasma cells. Immunoelectrophoresis of the CSF revealed monoclonal IgA-k type protein. A diagnosis of central nervous system (CNS)relapse was made. The patient died of pneumonia two months after relapse. It should be kept in mind that CNS relapse can occur during hematological remission in patients with multiple myeloma including PCL.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2010; 37(4):743-6.
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    ABSTRACT: The development of Burkitt's lymphoma (BL) is uncommon in elderly people. Most treatment-related hematological malignancies are of a myeloid lineage. Only a few cases with BL secondary to cancer treatment have been described. We report a rare case of an elderly patient with radiotherapy-related BL. A 71-year-old Japanese man, who had a past history of oropharyngeal cancer treated with local irradiation 15 years ago, presented with a left mandibular mass in December 2004. A partial mandibulectomy disclosed pathological features consistent with BL. Although the patient was initially treated with intensive chemotherapy, the development of complications precluded further anticancer drug treatment. Rituximab was administered once weekly for 5 consecutive weeks, with resolution of the mandibular mass. He remained in remission without further lymphoma treatment for more than 3 years after diagnosis. Rituximab monotherapy should be considered as a therapeutic option for elderly patients with BL.
    Acta Haematologica 10/2009; 122(4):211-5. DOI:10.1159/000253028 · 1.12 Impact Factor
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    ABSTRACT: We report a rare case of human immunodeficiency virus (HIV)- and human herpes virus-8 (HHV-8)-negative primary effusion lymphoma (PEL)-like lymphoma presenting with lymphomatous effusions complicated by cardiac tamponade. A 68-year-old woman was hospitalized with generalized weakness in June 2006. Echocardiogram revealed the presence of pericardial effusion and she had the signs of cardiac tamponade. Urgent pericardial drainage relieved her symptoms. Chest computed tomography showed bilateral pleural effusions along with pericardial effusion. Cytologic findings of both effusions were suggestive of malignancies, including malignant lymphoma. Immunocytochemical studies with a panel of antibodies, including CD20 and CD79a, could not provide a definite diagnosis. Flow cytometric analysis of pleural effusion revealed that tumor cells were positive for CD10 and CD19, but negative for CD20, CD23, surface immunoglobulin, and T-cell associated antigens. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. Polymerase chain reaction proved to be negative for HHV-8. The serology test for HIV was negative. After a diagnosis of HHV-8-negative PEL-like lymphoma, she was treated with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisolone). However, she died of progressive lymphoma 7 months after the diagnosis. PEL-like lymphomas are of B-cell origin. In some cases of PEL-like lymphoma, tumor cells may be negative for representative markers of B-cell phenotype such as CD20 and CD79a.
    Gan to kagaku ryoho. Cancer & chemotherapy 08/2009; 36(7):1195-8.
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    ABSTRACT: Extranodal adult T-cell leukemia/lymphoma (ATLL) of the head and neck is a rare disease. We studied the clinicopathological features of nine patients with ATLL involving extranodal head and neck sites and conducted a literature review. Six patients presented with extranodal mass of the head and neck, whereas three had disseminated diseases. Tumors involved the parotid gland, sinonasal tract, masseter muscle, mandible and skull. Histopathology included diffuse pleomorphic-type (with angiocentric features), Hodgkin-like and anaplastic large cell-type. Five patients with localised disease showed prolonged survival regardless of unfavourable histology and/or aberrant provirus status, including integration of multiple copies or defective provirus. Patients with localised disease documented in the literature, including our study series, had a reduced frequency of elevated lactate dehydrogenase, no hypercalcemia and longer survival. ATLL should be included in the differential diagnosis of extranodal head and neck lymphoma. Localised extranodal ATLL of the head and neck may exhibit indolent clinical behaviours.
    Leukemia & lymphoma 03/2009; 50(2):187-95. DOI:10.1080/10428190802702383 · 2.89 Impact Factor
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    ABSTRACT: We report a rare case of primary cutaneous diffuse large B-cell lymphoma (DLBCL) with Burkitt-like morphology. A 54-year-old man presented with multiple subcutaneous tumors. Pathological examination showed morphological features resembling Burkitt or Burkitt-like lymphoma (BL/BLL) with high MIB-1 positivity. Cytogenetic studies revealed no 8q24/c-myc translocation. After the diagnosis of Burkitt-like DLBCL, the patient was treated with CODOX-M chemotherapy (cyclophosphamide, doxorubicin, vincristine, cytarabine and methotrexate), which led to durable remission. The present case suggests that short-term, high-intensity chemotherapy used for BL/BLL may be appropriate for primary cutaneous Burkitt-like DLBCL, as well as systemic lymphoma with Burkitt-like morphology.
    Internal Medicine 02/2009; 48(6):475-8. DOI:10.2169/internalmedicine.48.1791 · 0.90 Impact Factor
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    ABSTRACT: Survivin, a member of the inhibitor of apoptosis protein (IAP) family, has been widely studied because of its aberrant expression in human cancer. Survivin has multiple functions, including cell-cycle regulation at mitosis, inhibition of apoptosis and caspase-independent cytoprotection. Clinical studies have shown that survivin is associated with resistance to treatment and its expression is linked to poor prognosis. Recent studies indicated that Ras pathways up-regulate survivin expression in hematopoietic cells. Here we analyzed downstream pathways of Ras in interleukin-3 (IL-3)-dependent Baf-3 murine-derived pro-B lymphocytic cells that express constitutively active Ras mutants, using signaling pathway-specific inhibitors. Both mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways are involved in the induction of survivin. Downstream of PI3-K, the signaling pathway is composed of two kinases, Akt and mammalian target of rapamycin (mTOR) pathways. In the downstream targets of PI3-K, mTOR but not Akt is responsible for survivin expression. Using a counterflow centrifugal elutriator, we observed G2/M phase-dominant survivin expression in Baf-3 cells. Interestingly, constitutively active Ras mutants also induced survivin in a cell cycle-dependent manner. Reporter assays of the survivin gene promoter revealed a transcriptional regulatory cis-acting region that is responsible for Ras signaling, indicating that Ras increases the transcription of the survivin gene through specific enhancer elements. These data illustrate the pathways regulating survivin expression by Ras. Ras activates the MAPK, PI3-K and mTOR pathways, and these signals enhance survivin transcription. Our data will provide the new information about mechanisms of survivin expression by Ras-signalling pathways.
    The Tohoku Journal of Experimental Medicine 10/2008; 216(1):25-34. DOI:10.1620/tjem.216.25 · 1.35 Impact Factor
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    ABSTRACT: Primary malignant lymphoma of the female genital tract is an extremely rare clinical entity. We report a case of primary non-Hodgkin lymphoma of the uterine cervix. A 68-year-old woman presented with abnormal genital bleeding in May 2002. A coloposcopic examination revealed a mass in the uterine cervix. Magnetic resonance imaging showed a bulky cervical tumor(7.5 x 8 cm)invading the right parametrium and adjacent levator ani muscle. Involvement of pelvic lymph nodes was also observed. The uterine lesion exhibited homogenous hypointensity on T1 weight image and isointense to hyperintense on T2-weight image. No other lesions were detected by the whole-body computed tomography, gallium scintigraphy, and bone marrow examination. Although cytology of the smear from the uterine cervix was nondiagnostic, the histologic examination of the punch biopsy material showed a diffuse proliferation of atypical lymphoid cells. Immunophenotypic studies revealed tumor cells were positive for CD19, CD20, CD30, and k-chain. A diagnosis of diffuse large B-cell lymphoma of the uterine cervix, clinical stage IIE was made. The patient was treated with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone(CHOP)chemotherapy followed by the involved field irradiation. She remains alive and free of disease more than 5 years after the diagnosis.
    Gan to kagaku ryoho. Cancer & chemotherapy 09/2008; 35(8):1423-5.
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    ABSTRACT: We report a Japanese case of human herpes virus-8 (HHV-8)-associated multicentric Castleman disease(MCD) complicated by hemophagocytic syndrome(HPS). A 60-year-old man presented with persistent fever and progressive pancytopenia in June 2004. On physical examination, anemia, icterus, hepatosplenomegaly, and generalized lymphadenopathy were detected. Laboratory findings showed elevated levels of serum ferritin and soluble interleukin-2 receptor. Anti-human immunodeficiency virus (HIV) antibody was negative. Bone marrow aspiration revealed a normocellular marrow with an increased number of hemophagocytic histiocytes. Biopsy of cervical lymph node disclosed pathological features compatible with the plasmablastic variant of Castleman disease. HHV-8 DNA was detected in the specimen from lymph node by polymerase chain reaction. Thus, the diagnosis of HHV-8-associated MCD complicated by HPS was made. The patient was treated with immunotherapy and subsequent chemotherapy. However, he died of bacterial sepsis after one-month therapy. This case report provides some evidence that HHV-8 may be a causative agent of MCD even in HIV-seronegative Japanese patients.
    Gan to kagaku ryoho. Cancer & chemotherapy 09/2008; 35(8):1431-4.
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    ABSTRACT: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoma and etiologically associated with human T-lymphotropic virus type 1 (HTLV-1). Patients with ATLL commonly present with leukemic changes, systemic lymphadenopathy, and/or extranodal lesion and have very poor prognosis. We describe a rare case of ATLL presenting as an isolated paranasal mass. Southern blot analysis of the biopsied specimens demonstrated multiple integration bands of HTLV-1 provirus of different intensities. Chemotherapy resulted in complete resolution of the paranasal mass. Thereafter, the patient showed an indolent clinical course with leukemic changes and pulmonary and cutaneous ATLL lesions and remains alive more than 5 years from diagnosis. ATLL should be included in the differential diagnosis of sinonasal lymphoma, although the event is rare. Multiple HTLV-1 provirus integrations of different intensities may be indicative of good prognosis for ATLL.
    Head & Neck 06/2008; 30(6):815-20. DOI:10.1002/hed.20730 · 2.64 Impact Factor
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    ABSTRACT: Primary extranodal involvement of Hodgkin lymphoma (HL) is rare. We report two HL patients presenting with exclusive or predominant lung involvement. In both cases, the results of transbronchial and/or CT-guided lung needle biopsy were indicative of granulomatous disease. Eventually, lymph node biopsy specimens revealed HL with nodular sclerosis type and lymphocyte-rich type, respectively. There were no specific symptoms, laboratory and imaging findings for pulmonary HL. A histological examination was required to confirm the diagnosis. Lung biopsy techniques such as transbronchial or percutaneous biopsy may be insufficient to allow diagnosis of HL. Pulmonary HL should be included in the differential diagnosis of lung involvement, even when the pathological evaluation of nonspecific inflammation was made from the biopsied specimens.
    Gan to kagaku ryoho. Cancer & chemotherapy 01/2008; 34(13):2279-82.
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    ABSTRACT: A new cell line, STR-428 was established from ascites tumor cells of a malignant effusion lymphoma patient without human herpes virus-8 (HHV-8) infection. STR-428 cells showed an immunophenotype of mature B-cells and produced few cytokines related to lymphomatous effusion. Karyotypic and genetic analysis revealed complex translocations including t(14;18)(q32;q21) effecting IgH/BCL2 and der(8)t(3;8)(q27;q24) involving c-MYC. STR-428 represents a unique, B-cell lymphoma cell line carrying concurrent rearrangement of BCL2 and c-MYC genes with features distinct from those of HHV-8-related primary effusion lymphoma. This cell line may be a valuable tool, other than HHV-8, to investigate the pathogenesis of primary lymphomatous effusion.
    Leukemia Research 10/2007; 31(9):1285-92. DOI:10.1016/j.leukres.2006.12.023 · 2.35 Impact Factor
  • Takashi Sonoki · Hiro Tatetsu · Akitoshi Nagasaki · Hiroyuki Hata ·

    International Journal of Hematology 09/2007; 86(2):196-8. DOI:10.1532/IJH97.07083 · 1.92 Impact Factor
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    ABSTRACT: Primary adrenal lymphoma (PAL) is very rare; the majority of cases reported previously were of B-cell origin. We report a rare case of primary adrenal adult T-cell leukemia/lymphoma (primary adrenal ATLL). ATLL is a highly aggressive T-cell type non-Hodgkin's lymphoma and etiologically associated with human T-cell lymphotropic virus 1 (HTLV-1). Most ATLL patients present with leukemia and widespread lymphadenopathy. A 37-year-old Japanese woman presented with back pain in January 2004. Examination showed no peripheral lymphadenopathy, circulating lymphoma cells, hepatosplenomegaly, and skin lesions. Imaging studies demonstrated large adrenal masses bilaterally. Subsequently, she underwent open adrenal biopsy and pathological diagnosis was confirmed as T-cell lymphoma. The serum antibody to HTLV-1 was positive. Southern blot analysis detected monoclonal integration of proviral DNA of HTLV-1 into host genome in the biopsy specimen. The diagnosis of ATLL arising in adrenal glands was established. Despite repeated systemic chemotherapy, the patient died of progressive disease in December 2004. ATLL could primarily involve the adrenal gland and this disease entity should be included in the differential diagnosis of adrenal mass lesions.
    American Journal of Hematology 08/2007; 82(8):748-52. DOI:10.1002/ajh.20856 · 3.80 Impact Factor
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    ABSTRACT: We report an extremely rare case of interdigitating dendritic cell sarcoma/tumor (IDCS). A 52-year-old man presented with a 2-week history of fever in January 2002. Physical examination revealed enlarged, painless right axillary lymph nodes, and hepatosplenomegaly. Whole-body computerized tomography showed enlarged lymph nodes in mediastinal, right axillary, abdominal para-aortic, ileum, and inguinal regions. Hepatosplenomegaly was also detected. In addition to abnormal liver function tests, serum levels of soluble interleukin-2 receptor and ferritin were elevated. Excisional biopsy of right axillary lymph node was performed in February 2002. Histological examination showed a diffuse proliferation of medium-to large-sized cells with round or oval nuclei and abundant cytoplasm. Spindle shape cells and Hodgkin-like giant cells were also seen. Immunohistochemically, the tumor cells expressed S-100 protein, CD 68, and CD 45 RO. They were negative for CD 1, CD 3, CD 15, CD 20, CD 21, CD 23, FDC, DRC, and p80. These findings were compatible with the diagnosis of IDCS. The patient was treated with polychemotherapy consisting of doxorubicin,cyclophosphamide, vincristine, and prednisone. However, he developed fungal pneumonia and died of respiratory failure 1 month after the start of treatment.
    Gan to kagaku ryoho. Cancer & chemotherapy 04/2007; 34(3):469-71.

  • International Journal of Hematology 03/2007; 85(2):95-6. DOI:10.1532/IJH97.06184 · 1.92 Impact Factor

  • Internal Medicine 02/2007; 46(22):1881-2. DOI:10.2169/internalmedicine.46.0069 · 0.90 Impact Factor
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    ABSTRACT: Cases of adult T-cell leukemia (ATL) with aberrant phenotypes have a very poor prognosis. We report the development of acute type, CD 8 positive ATL in a carrier of hepatitis B virus (HBV). The patient was treated with a combination of lamivudine and chemotherapy and consequently had longer-term survival than those reported previously. A 64-year-old(corrected 65-year-old) man was referred to our hospital in January 2002 because of ascites and abdominal tumor. He was positive for anti-HTLV-1 antibody and HBV surface antigen. Generalized computed tomography demonstrated bilateral pleural effusion, abdominal mass, and massive ascites. Cytological examination of ascitis revealed numerous atypical lymphoid cells,which were positive for CD 2, CD 5, CD 8, and CD 25. Monoclonal integration of HTLV-1 provirus was detected by Southern blot analysis on DNA extracted from lymphoid cells. A diagnosis of acute type, CD 8 positive ATL was made. Lamivudine was administered for prevention of chemotherapy induced HBV reactivation. Subsequently, he was treated with 6 cycles of CHOP and went into remission. He maintained clinical remission during a follow-up of 13 months and then relapsed. Further salvage therapies were provided with a transient effect. He died of sepsis in February 2004. The overall survival time of this patient was 25 months. It is possible that lamivudine combined with chemotherapy may have had a therapeutic effect on ATL in this case.
    Gan to kagaku ryoho. Cancer & chemotherapy 06/2006; 33(5):683-6.

  • Internal Medicine 02/2006; 45(2):113-4. · 0.90 Impact Factor

  • Internal Medicine 01/2006; 45(2):113-114. DOI:10.2169/internalmedicine.45.1559 · 0.90 Impact Factor
  • Akitoshi Nagasaki · Wakako Takamine · Nobuyuki Takasu ·

    Clinical Nutrition 11/2005; 24(5):864-5. DOI:10.1016/j.clnu.2005.06.009 · 4.48 Impact Factor

Publication Stats

1k Citations
180.07 Total Impact Points


  • 2002-2009
    • University of the Ryukyus
      • • Department of Endocrinology and Metabolism
      • • Second Department of Internal Medicine
      • • Faculty of Medicine
      Okinawa, Okinawa, Japan
  • 1994-2003
    • Kumamoto University
      • • Department of Molecular Genetics
      • • School of Medicine
      Kumamoto, Kumamoto, Japan