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Sugie T.,Kyoto University | Sawada T.,Showa University | Tagaya N.,Dokkyo Medical University | Kinoshita T.,National Cancer Center Hospital | And 7 more authors.
Annals of Surgical Oncology | Year: 2013

Purpose: To assess the diagnostic performance of sentinel lymph node (SLN) biopsy using the indocyanine green (ICG) fluorescence method compared with that using the blue dye method, a prospective multicenter study was performed. Methods: Patients with T1-3 primary breast cancer without clinical lymph node involvement were included in this study. ICG as a fluorescence-emitting source and indigo carmine as blue dye were injected into the subareolar area. Extracted lymph nodes were examined to identify the first, second, and other SLNs. The identified nodes were classified according to the ICG fluorescence signal and blue dye uptake. Results: Ninety-nine eligible patients were included in this study. The ICG fluorescence method identified an average of 3.4 SLNs (range, 1-8) in 98 of 99 patients (detection rate, 99 %). The number of lymph nodes identified by the fluorescence method was significantly higher than that identified by the blue dye method (p < 0.001). SLN involvement was identified in 20 % (20 of 99) of patients, all of whom tested positive for the first SLN. In 16 patients, complete axillary lymph node dissection (ALND) was performed. In 25 % (4 of 16) of these patients, axillary metastases were identified; however, no axillary involvement was found in 8 patients with only one involved node, which was isolated as the first SLN. Conclusions: High rate of SLN detection was achieved using the ICG fluorescence method. The first SLN identified by fluorescence imaging provides an exact indication of the axillary status. Therefore, the ICG fluorescence method provides precise information required to avoid unnecessary ALND. © 2013 Society of Surgical Oncology.


Tabata C.,Hyogo College of Medicine | Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Nakano T.,Hyogo College of Medicine
Clinical and Experimental Immunology | Year: 2010

Pulmonary fibrosis is characterized by progressive worsening of pulmonary function leading to a high incidence of death. Currently, however, there has been little progress in therapeutic strategies for pulmonary fibrosis. There have been several reports on cytokines being associated with lung fibrosis, including interleukin (IL)-6 and transforming growth factor (TGF)-β1. We reported recently that two substances (ATRA and thalidomide) have preventive effects on pulmonary fibrosis by inhibiting IL-6-dependent proliferation and TGF-β1-dependent transdifferentiation of lung fibroblasts. Rheumatoid arthritis is a chronic autoimmune disorder, and its pathogenesis is also characterized by an association with several cytokines. It has been reported that calpain, a calcium-dependent intracellular cysteine protease, plays an important role in the progression of rheumatoid arthritis. In this study, we examined the preventive effect of Calpeptin, a calpain inhibitor, on bleomycin-induced pulmonary fibrosis. We performed histological examinations and quantitative measurements of IL-6, TGF-β1, collagen type Ia1 and angiopoietin-1 in bleomycin-treated mouse lung tissues with or without the administration of Calpeptin. Calpeptin histologically ameliorated bleomycin-induced pulmonary fibrosis in mice. Calpeptin decreased the expression of IL-6, TGF-β1, angiopoietin-1 and collagen type Ia1 mRNA in mouse lung tissues. In vitro studies disclosed that Calpeptin reduced (i) production of IL-6, TGF-β1, angiopoietin-1 and collagen synthesis from lung fibroblasts; and (ii) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis. These data suggest the clinical use of Calpeptin for the prevention of pulmonary fibrosis. © 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.


Tabata R.,Hyogo Prefectural Tsukaguchi Hospital
Journal of clinical and experimental hematopathology : JCEH | Year: 2013

Here, we report a rare case of double-hit lymphoma, demonstrating t(6;14;18)(p25;q32;q21), suggesting two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2. The present case had a rare abnormal chromosome, t(6;14;18)(p25;q32;q21), independently, in addition to known dual-hit chromosomal abnormalities, t(14;18)(q32;q21) and t(8;22)(q24;q11.2). Lymph node was characterized by a follicular and diffuse growth pattern with variously sized neoplastic follicles. The intrafollicular area was composed of centrocytes with a few centroblasts and the interfollicular area was occupied by uniformly spread medium- to large-sized lymphocytes. CD23 immunostaining demonstrated a disrupted follicular dendritic cell meshwork. The intrafollicular tumor cells had a germinal center phenotype with the expression of surface IgM, CD10, Bcl-2, Bcl-6, and MUM1/IRF4. However, the interfollicular larger cells showed plasmacytic differentiation with diminished CD20, Bcl-2, Bcl-6, and positive intracytoplasmic IgM, and co-expression of MUM1/IRF4 and CD138 with increased Ki-67-positive cells (> 90%). MUM1/IRF4 has been found to induce c-MYC expression, and in turn, MYC transactivates MUM1/IRF4, creating a positive autoregulatory feedback loop. On the other hand, MUM1/IRF4 functions as a tumor suppressor in c-MYC-induced B-cell leukemia. The present rare case arouses interest in view of the possible "dual" activation of both c-MYC and MUM1/IRF4 through two independent dual-translocations, c-MYC/BCL-2 and IRF4/BCL-2.


Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Tabata C.,Hyogo College of Medicine
International Immunopharmacology | Year: 2014

Large granular lymphocyte (LGL) leukemia is characterized by a clonal proliferation of large-sized lymphocytes with prominent large azurophilic cytoplasmic granules. Although most cases of T-LGL leukemia are indolent and asymptomatic during the course of the disease, some present with pure red cell aplasia (PRCA) and require therapy. We here reported a case of T-LGL leukemia complicated by PRCA in which anemia was resistant to cyclosporine and had been controlled for several years by cyclophosphamide; however, progressive anemia developed despite the administration of cyclophosphamide, but was ameliorated by the re-administration of cyclosporine. The present case demonstrated the 3 different phases of T-LGL proliferation associated with anemia (1st, T-LGL leukemia; 2nd, polyclonal T-LGL expansion; 3rd, myelodysplastic syndrome). We also showed that cyclophosphamide was effective when PRCA was caused by increased numbers of LGL, whereas cyclosporine was administered when hypoplastic myelodysplastic syndrome was suspected as the main cause of anemia. Repetitive bone marrow examinations should be performed throughout the course of T-LGL in order to monitor combined myelodysplastic syndrome. © 2014 Elsevier B.V. All rights reserved.


Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Tabata C.,Hyogo College of Medicine | Kita Y.,Hyogo Prefectural Tsukaguchi Hospital
Journal of Thrombosis and Thrombolysis | Year: 2013

Sometimes it is difficult to distinguish anti-phospholipid syndrome (APS) from immune thrombocytopenic purpura (ITP). Here we present successful management of ITP with anti-phospholipid antibodies, complicated by acute coronary syndrome (ACS), using CT coronary angiography (CTCA). The therapy for ITP may be changed for APS if ACS was thromboembolic event. As coronary angiography is thought to be very dangerous for patients with severe thrombocytopenia, noninvasive CTCA was desirable for our patient. Since no occlusion or narrowing was observed in CTCA, she has been safely treated as ITP with immunosuppressive agents throughout the course without antiplatelet or antithrombin therapy. © 2012 Springer Science+Business Media, LLC.


Yamada S.,Hyogo College of Medicine | Tabata C.,Hyogo College of Medicine | Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Fukuoka K.,Hyogo College of Medicine | Nakano T.,Hyogo College of Medicine
Clinical Chemistry and Laboratory Medicine | Year: 2011

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin associated with asbestos exposure. MPM has a limited response to conventional chemotherapy and radiotherapy, so early diagnosis of MPM is very important. This study investigated the pleural effusion mesothelin levels in patients with MPM and compared them to those of a population with a non-malignant pleuritis or lung cancer involving malignant pleural effusion. Methods: The pleural effusion mesothelin concentrations were measured in 45 MPM patients and 53 non-MPM individuals (24 individuals with non-malignant pleural effusions and 29 individuals with lung cancer involving malignant pleural effusion). Results: This study demonstrated that patients with MPM had significantly higher pleural effusion mesothelin levels than a population with non-malignant pleuritis or lung cancer involving malignant pleural effusion. The difference in overall survival between the groups with pleural effusion mesothelin levels lower and higher than the assumed cut-off of 10 nM was significant. Conclusions: The data suggest that the pleural effusion mesothelin concentration could be useful as an aid for the diagnosis of MPM. © 2011 by Walter de Gruyter Berlin Boston.


Takeuchi K.,National Hospital Organization | Tsujino T.,National Hospital Organization | Yabuta M.,Hyogo Prefectural Tsukaguchi Hospital | Kitazawa S.,Ehime University
European Journal of Gynaecological Oncology | Year: 2012

Background: Ichthyosis uteri is an uncommon entity in which the entire endometrium is replaced by stratified squamous epithelium. Though the condition often is considered as benign, dysplastic changes have been reported. Case: We describe herein an exceedingly rare case of primary squamous cell carcinoma of the endometrium (PSCCE) associated with extensive ichthyosis uteri with chronic pyometra, who presented with blood-stained vaginal discharge of six-seven months duration. Although repeated endometrial biopsies revealed only strips of stratified squamous epithelium showing moderate to severe dysplastic changes, the tumor markers and magnetic resonance imaging strongly suggested advanced uterine body malignancy. Exploratory laparotomy was performed, and histologic findings of the superficial layer were consistent with ichthyosis uteri; in contrast the lesion of invasive squamous cell carcinoma was located in the deeper layer and lymph nodes. No dysplastic changes of the cervix were noted. Conclusions: It is suggested that PSCCE could be associated with pre-existing ichthyosis uteri and deeper biopsies should be performed for the accurate preoperative diagnosis of cases with chronic pyometra.


Maeda R.,Hyogo College of Medicine | Tabata C.,Hyogo College of Medicine | Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Eguchi R.,Hyogo College of Medicine | And 2 more authors.
Antioxidants and Redox Signaling | Year: 2011

Malignant pleural mesothelioma (MPM), an asbestos-related aggressive malignant tumor of mesothelial origin, shows limited response to therapy and overall survival remains very poor. Reactive oxygen species play an important role in asbestos toxicity. Here, we found that the patients with MPM had significantly higher serum levels of thioredoxin-1 (TRX) than control population. The patients with advanced-stage MPM showed higher levels of TRX than those with early-stage MPM. The difference in overall survival between the groups with lower and higher serum TRX levels was significant. Our data suggest that serum TRX concentration could be a useful clinical marker for MPM. © 2011 Mary Ann Liebert, Inc.


Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Iwama H.,Hyogo Prefectural Tsukaguchi Hospital | Tabata C.,Hyogo Prefectural Tsukaguchi Hospital | Yasumizu R.,Hyogo Prefectural Tsukaguchi Hospital | Kojima M.,Hyogo Prefectural Tsukaguchi Hospital
Journal of clinical and experimental hematopathology : JCEH | Year: 2014

We report a rare primary splenic diffuse large B-cell lymphoma demonstrating CD5(+) and CD23(+) with very low CD20 expression. The only lesion was detected in the spleen, which was extremely enlarged with multiple large white-colored nodules. The lesion was characterized by a diffuse growth pattern of medium- to large-sized lymphoma cells with abundant cytoplasm. Immunohistochemical and flow cytometric study demonstrated that the lymphoma cells were negative for CD2, CD3, CD4, CD8, CD10, CD56, CD138, ALK-1, λ-light chain, and cyclin-D1, and positive for CD5, CD19, CD23, CD25, CD38, CD43, CD79a, IgM, IgD, κ-light chain, BCL2, BCL6, BOB. 1, Oct-2, Pax5, and MUM-1. CD20 was very weakly positive immunohistochemically, and negative by flow cytometric analysis. These findings resembled Richter syndrome, although chronic lymphocytic leukemia was not preexisting. Extremely poor outcome might be supposed because the effect of rituximab might be quite limited since CD20 was very weakly positive, in addition to an inferior prognosis of both CD20(-) and CD5(+) diffuse large B-cell lymphoma. Careful management is thus necessary.


Tabata C.,Hyogo College of Medicine | Shibata E.,Hyogo College of Medicine | Tabata R.,Hyogo Prefectural Tsukaguchi Hospital | Kanemura S.,Hyogo College of Medicine | And 5 more authors.
BMC Cancer | Year: 2013

Background: Malignant pleural mesothelioma (MPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to conventional chemotherapy and radiotherapy. Therefore, diagnosing MPM early is very important. Some researchers have previously reported that high-mobility group box 1 (HMGB1) was correlated with pulmonary fibrosis. MPM involves the malignant transformation of mesothelial cells, which originate from mesenchymal cells similar to lung fibroblasts. Here, we investigated serum levels of HMGB1 in patients with MPM and compared them with those of a population that had been exposed to asbestos without developing MPM.Methods: HMGB1 production from MPM cell lines was measured using ELISA. Serum HMGB1 levels were also examined in 61 MPM patients and 45 individuals with benign asbestos-related diseases.Results: HMGB1 concentrations of 2 out of 4 MPM cell lines were higher than that of normal mesothelial cell line, Met-5A. We demonstrated that patients with MPM had significantly higher serum levels of HMGB1 than the population who had been exposed to asbestos but had not developed MPM. The difference in overall survival between groups with serum HMGB1 levels that were lower and higher than assumed cut-off values was significant.Conclusions: Our data suggest that serum HMGB1 concentration is a useful prognostic factor for MPM. © 2013 Tabata et al.; licensee BioMed Central Ltd.

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