Hirotsugu Kohrogi

Kumamoto University, Kumamoto, Kumamoto, Japan

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Publications (119)314.31 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pseudomonas aeruginosa (P. aeruginosa) bacteremia occurs mainly in immunocompromised patients. However, P. aeruginosa bacteremia in immunocompetent patients has also been reported. The aim of the study is to evaluate the clinical characteristics of P. aeruginosa bacteremia in relation to the immune status of the patients. The medical records of 126 adult patients with P. aeruginosa bacteremia in Nagasaki university hospital were retrospectively reviewed between January 2003 and December 2012. Of 126 patients with P. aeruginosa bacteremia, 60 patients (47.6%) were classified as immunocompetent. Mortality in immunocompetent patients tended to be lower than immunocompromised patients (7-day mortality, 8% vs 30%, p <0.01; 30-day mortality, 23% vs 39%, p = 0.053). Multivariate analysis showed that higher SOFA score (hazard ratio [HR]: 1.27, p <0.01) and underlying malignancies (HR: 3.33, p <0.01) were independently associated with 30-day mortality. Initial antibiotic therapy (HR: 0.21, p <0.01) and patients' immune status (HR: 0.29, p =0.02) also had a significant impact on survival. However, there was a significant interaction between these two variables (p = 0.03 for interaction). A subgroup analysis showed that only in immunocompromised patients, initial appropriate antibiotic therapy was associated with lower mortality (30-day mortality 20.5% vs 66.7%, p <0.01 by log-rank test).
    06/2015; DOI:10.7883/yoken.JJID.2014.573
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    ABSTRACT: Paragonimiasis is a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat and this infection is endemic in Asia. We herein report two cases of pulmonary Paragonimus westermani infection associated with elevated levels of serum immunoglobulin (Ig) G4 and dense infiltration of IgG4-positive plasma cells in the lung lesions. Treatment with praziquantel resolved the pulmonary lesions and decreased the serum levels of IgG4. IgG4-related disease is a systemic disease occasionally involving the lungs and leads to increased serum levels of IgG4. Our findings suggest that P. westermani infection requires a differential diagnosis from IgG4-related diseases and the serum IgG4 level may be a potentially useful marker of P. westermani infection.
    06/2015; DOI:10.1002/rcr2.110
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    ABSTRACT: Background. Pulmonary blastoma is a rare lung tumor similar to fetal lung tissues. Surgical resection at early stage is more curative than other treatments, but there is no standard treatment in unresectable cases. We show a case treated with carboplatin and paclitaxel plus bevacizumab. Case. A 68-year-old man received surgical resection and was diagnosed with biphasic pulmonary blastoma (pT3N0M0 stage IIB). Metastasis to the spleen was detected six weeks after the surgery. Carboplatin, paclitaxel, and bevacizumab were administered and showed an effect on the metastasis. Four courses of the chemotherapy were completed, but a metastasis was found and the metastatic tumor in the spleen was enlarged. After that, chemotherapy was not effective afterward and he died of the progression of biphasic pulmonary blastoma on the 292nd day of illness. Conclusion. In this case, chemotherapy with carboplatin and paclitaxel plus bevacizumab was temporarily efficacious for biphasic pulmonary blastoma.
    05/2015; 2015:1-4. DOI:10.1155/2015/842621
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    ABSTRACT: Crizotinib is an oral small-molecule anaplastic lymphoma kinase (ALK) tyrosine-kinase inhibitor for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). A 63-year old woman with postoperative relapsed ALK-positive NSCLC was treated with crizotinib. Erythema multiforme (EM) occurred one week after initiation of crizotinib therapy. Skin biopsy specimen showed compatible drug eruption. The discontinuation of crizotinib improved her eruption within one week. This report presented the first case of crizotinib-associated EM, which is the preclinical stage of Stevens-Johnson syndrome. Although crizotinib is clinically available, we should be aware of its potential severe skin adverse event.
    01/2015; 9(2):142-3. DOI:10.5582/ddt.2015.01019
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    ABSTRACT: Ventilator-associated pneumonia (VAP) due to Pseudomonas aeruginosa has a high recurrence rate. We report a case of chronic P. aeruginosa infection with recurrent episodes of VAP in a patient with acute respiratory distress syndrome, which was successfully controlled by inhaled tobramycin therapy. A 66-year-old man injured his arm at work and underwent emergency surgery. He developed acute respiratory distress syndrome complicated by VAP and required long-term mechanical ventilation. On the 57th day of ICU stay, P. aeruginosa was isolated from endotracheal aspirates. He subsequently developed recurrent episodes of VAP at short intervals, resulting in prolonged mechanical ventilation. On the 192th day of ICU stay, aerosolized tobramycin therapy was started to treat the chronic P. aeruginosa infection, after which endotracheal tube aspirates showed a rapid decrease in the density of P. aeruginosa and the episodes of VAP reduced in frequency. The patient was successfully weaned off the ventilator on the 260th day of ICU stay. Inhaled tobramycin therapy is safe and may be useful for the prevention of recurrent VAP due to P. aeruginosa.
    Nihon Shuchu Chiryo Igakukai zasshi 01/2015; 22(2):122-126. DOI:10.3918/jsicm.22.122
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    ABSTRACT: Background. Combined large cell neuroendocrine carcinoma (LCNEC) is a rare histological type of primary lung cancer. Case. We experienced the case of a 60-year-old man who had a solid round lung nodule measuring 16×11 mm located in the right S6. The patient underwent radical surgery, and histopathology revealed LCNEC combined with adenocarcinoma (Ad) and squamous cell carcinoma (Sq), defined as pathological T1aN1M0 stage IIA disease. He received adjuvant chemotherapy with cisplatin (60 mg/m2, day 1) and irinotecan (60 mg/m2, day 1, 8, 15) for a total of four cycles and has since been followed without evidence of recurrence for one year after the surgery. Conclusions. We herein present an extremely rare case of cancer consisting of combined LCNEC with both Ad and Sq.
    Haigan 01/2015; 55(2):89-92. DOI:10.2482/haigan.55.89
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    ABSTRACT: Objectives: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed. Methods: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. Results: Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. Conclusions: For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities. © 2014 S. Karger AG, Basel.
    Oncology 12/2014; 88(4):201-207. DOI:10.1159/000369255 · 2.61 Impact Factor
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    ABSTRACT: A 67-year-old man suffering from esophageal cancer was admitted to our hospital complaining of dyspnea and hypoxemia. He had been treated with cisplatin, docetaxel, and fluorouracil combined with radiotherapy. Chest computed tomography revealed bilateral ground-glass opacity, and bronchoalveolar lavage fluid showed increased eosinophils. Two episodes of transient eosinophilia in peripheral blood were observed after serial administration of anticancer drugs before the admission, and drug-induced lymphocyte stimulation test to cisplatin was positive. Thus cisplatin-induced eosinophilic pneumonia was suspected, and corticosteroid was effectively administered. To our knowledge, this is the first reported case of cisplatin-induced eosinophilic pneumonia.
    11/2014; 2014:209732. DOI:10.1155/2014/209732
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    ABSTRACT: Identification of peptides that activate both tumor-specific helper T (Th) cells and cytotoxic T lymphocytes (CTLs) are important for the induction of effective antitumor immune responses. We focused on a long peptide (LP) derived from lymphocyte antigen 6 complex locus K (LY6K) encompassing both candidate Th epitopes and a known CTL epitope. Using IFNγ ELISPOT assays as a marker of activated T cells, we studied the immunogenicity and cross-priming potential of LY6K-LP, assaying human immune cell responses in vitro and immunologic activities in HLA-A24 transgenic mice in vivo. We identified LY6K172-191-LP as an effective immunogen spanning naturally processed epitopes recognized by T helper type 1 (Th1) cells and CTLs. LY6K-specific CTLs were induced through cross-presentation of LY6K172-191-LP in vitro and in vivo. In addition, LY6K172-191-LP enhanced induction of LY6K-specific CTLs among the peripheral blood mononuclear cells (PBMCs) of head-and-neck malignant tumor (HNMT) patients. LY6K172-191-LP-specific Th1 immunologic response following 1 week in vitro stimulation of PBMCs with LY6K172-191-LP were detected in 16 of 21 HNMT patients (76%) vaccinated with CTL-epitope peptides and 1 of 11 HNMT patients (9%) prior to vaccination, but not in 9 healthy donors. Our results are the first to demonstrate the presence of LY6K-specific Th1 cell responses in HNMT patients and underscore the possible utility of LY6K172-191-LP for the induction and propagation of both LY6K-specific Th1 cells and CTLs.
    OncoImmunology 03/2014; 3(3). DOI:10.4161/onci.28100 · 6.28 Impact Factor
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    ABSTRACT: We recently identified a novel cancer-testis antigen, cell division cycle associated 1 (CDCA1) using genome-wide cDNA microarray analysis, and CDCA1-derived cytotoxic T lymphocyte (CTL)-epitopes. In this study, we attempted to identify CDCA1-derived long peptides (LPs) that induce both CD4+ helper T (Th) cells and CTLs. We combined information from a recently developed computer algorithm predicting HLA class II-binding peptides with CDCA1-derived CTL-epitope sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate CDCA1-LPs encompassing both Th cell epitopes and CTL-epitopes. We studied the immunogenicity of CDCA1-LPs and the cross-priming potential of LPs bearing CTL-epitopes in both human in vitro and HLA-class I transgenic mice in vivo. Then we analyzed the Th cell response to CDCA1 in head-and-neck cancer (HNC) patients before and after vaccination with a CDCA1-derived CTL-epitope peptide using IFN-γ enzyme-linked immunospot assays. We identified two CDCA1-LPs, CDCA1(39–64)-LP and CDCA1(55–78)-LP, which encompass naturally processed epitopes recognized by Th cells and CTLs. CDCA1-specific CTLs were induced through cross-presentation of CDCA1-LPs in vitro and in vivo. In addition, CDCA1-specific Th cells enhanced induction of CDCA1-specific CTLs. Furthermore, significant frequencies of CDCA1-specific Th cell responses were detected after short-term in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with CDCA1-LPs in HNC patients (CDCA1(39–64)-LP, 74%; CDCA1(55–78)-LP, 68%), but not in healthy donors. These are the first results demonstrating the presence of CDCA1-specific Th cell responses in HNC patients and underline the possible utility of CDCA1-LPs for propagation of both CDCA1-specific Th cells and CTLs.
    International Journal of Cancer 01/2014; 134(2):352-66. DOI:10.1002/ijc.28376 · 5.01 Impact Factor
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    ABSTRACT: Background. Pleomorphic carcinoma is a histological subset of lung cancer in the revised classification proposed by the WHO. Pulmonary pleomorphic carcinoma is rare, representing only 0.1-0.4% of all malignant tumors of the lung, and the recommended therapy has yet to be defined. Gingival metastasis is very rare, comprising only 1-3% of oral malignant tumors. We experienced a case of metastasis of pulmonary pleomorphic carcinoma that was successfully treated with concurrent chemoradiotherapy. Case. A 76-year-old man with pain and hemorrhage in the right maxillary molar gingiva was referred to the oral and maxillofacial surgery department of our hospital. Positron emission tomography with 18-fluorodeoxy-glucose (FDG-PET) and CT revealed a nodule in the left inferior lobe and left hilar and mediastinal lymph nodes, with a high maximum standardized uptake value (SUVmax). A biopsy of the mediastinal lymph node and gingival tumor was performed for a further evaluation. The histopathological analysis indicated the presence of pulmonary pleomorphic carcinoma with gingival metastasis. In order to improve the deformity in the patient&apos;s facial appearance and relieve the pain and hemorrhage caused by the gingival metastasis, we administered palliative radiotherapy for gingival metastasis with two cycles of chemotherapy consisting of carboplatin and paclitaxel. Although the treatment dramatically improved the gingival metastasis and the patient&apos;s facial aesthetics, his general condition gradually worsened in association with progression of the mediastinal lesion and other metastases and he ultimately died 54 days after the therapeutic intervention. Conclusions. In the present case, the gingival metastasis within the irradiation field was successfully treated, whereas the primary lesion and other metastases located outside the irradiation field rapidly progressed despite the administration of chemotherapy. These results suggest that radiotherapy for gingival metastasis of pulmonary pleomorphic carcinoma is effective and subsequently improves the patient&apos;s oral function and facial aesthetics.
    Haigan 01/2014; 54(7):969-973. DOI:10.2482/haigan.54.969
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    ABSTRACT: PURPOSE: To identify long peptides (LPs) derived from a novel tumor-associated antigen (TAA), kinesin family member 20A (KIF20A), which induce tumor-specific T-helper type 1 (Th1) cells and CTLs. EXPERIMENTAL DESIGN: We combined information from a recently developed computer algorithm predicting HLA class II-binding peptides with KIF20A-derived CTL-epitope sequences presented by HLA-A2 (A*02:01) or HLA-A24 (A*24:02) to select candidate promiscuous Th1 cell epitopes containing CTL-epitopes. Peripheral blood mononuclear cells (PBMC) derived from healthy donors or patients with head-and-neck malignant tumor (HNMT) were used to study the immunogenicity of KIF20A-LPs, and the in vitro cross-priming potential of KIF20A-LPs bearing CTL-epitopes. We used HLA-A24 transgenic mice to address whether vaccination with KIF20A-LP induces efficient cross-priming of CTLs in vivo. The Th1 cell response to KIF20A-LPs in HNMT patients receiving immunotherapy with TAA-derived CTL-epitope peptides was analyzed using IFN-γ enzyme-linked immunospot assays. RESULTS: We identified promiscuous KIF20A-LPs bearing naturally processed epitopes recognized by CD4(+) T-cells and CTLs. KIF20A-specific CTLs were induced by vaccination with a KIF20A-LP in vivo. KIF20A expression was detected in 55% of HNMT by immunohistochemistry, and significant frequencies of KIF20A-specific Th1 cell responses were detected after short-term in vitro stimulation of PBMCs with KIF20A-LPs in 50% of HNMT patients, but not in healthy donors. Furthermore, these responses were associated with KIF20A expression in HNMT tissues. CONCLUSIONS: These are the first results demonstrating the presence of KIF20A-specific Th1 cell responses in HNMT patients and underline the possible utility of KIF20A-LPs for propagation of Th1 cells and CTLs.
    Clinical Cancer Research 05/2013; 19(16). DOI:10.1158/1078-0432.CCR-13-0197 · 8.19 Impact Factor
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    ABSTRACT: Quorum sensing (QS) in Pseudomonas aeruginosa (P. aeruginosa) regulates the production of many virulence factors and plays an important role in the pathogenesis of P. aeruginosa infection. N-Acyl homoserine lactones (AHL) are major QS signal molecules. Recently, a novel AHL-lactonase enzyme, AiiM, has been identified. The aim of this study was to evaluate the effect of AiiM on the virulence of P. aeruginosa in a mouse model of acute pneumonia.We developed a P. aeruginosa PAO1 strain harbouring an AiiM-expressing plasmid. The production of several virulence factors by the AiiM-expressing strain was examined. Mice were intratracheally infected with an AiiM-expressing PAO1 strain. Lung histopathology, bacterial burden, and bronchoalveolar lavage (BAL) were assessed at 24 h post-infection.AiiM expression in PAO1 reduced production of AHL-mediated virulence factors and attenuated cytotoxicity against human lung epithelial cells. In a mouse model of acute pneumonia, AiiM expression reduced lung injury and greatly improved the survival rates. The levels of pro-inflammatory cytokines and myeloperoxidase activity in BAL fluid were significantly lower in mice infected with AiiM-expressing PAO1.Thus, AiiM can strongly attenuate P. aeruginosa virulence in a mammalian model and is a potential candidate for use as a therapeutic agent against P. aeruginosa infection.
    Antimicrobial Agents and Chemotherapy 05/2013; 57(8). DOI:10.1128/AAC.00456-13 · 4.45 Impact Factor
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    ABSTRACT: Amiodarone pulmonary toxicity (APT) is the most serious side effect of amiodarone. Although severe APT, such as ARDS, is rare, mortality of severe APT is high. Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is a medical device that reduces blood endotoxin levels in sepsis. Recent reports have shown that PMX-DHP improves oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis and drug-induced severe interstitial pneumonia. Here, we present a case study of a patient with severe APT treated with PMX-DHP with complete recovery. The patient rapidly developed respiratory failure and required mechanical ventilation. Despite corticosteroid pulse therapy, no clinical improvement was noted. PMX-DHP was then started, and severe respiratory failure improved with reduction of serum levels of amiodarone and its metabolite monodesethylamiodarone. The patient was weaned from mechanical ventilation and has done well without recurrence. To our knowledge, this is the first reported case of PMX-DHP therapy for severe APT. We speculate that PMX-DHP could be a new treatment strategy for severe APT.
    Chest 04/2013; 143(4):1146-50. DOI:10.1378/chest.12-0994 · 7.13 Impact Factor
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    ABSTRACT: Human T-cell leukemia virus type 1 (HTLV-1) carriers are rarely subject to inflammatory disorders in multiple organs, other than the well-known complication, adult T-cell leukemia/lymphoma (ATLL). HTLV-1 associated bronchiolo-alveolar disorder (HABA) has been proposed as an immune mediated pulmonary reaction seen rarely in HTLV-1 carriers. The reported clinico-pathological patterns of HABA are diffuse panbronchiolitis (DPB) and lymphoid interstitial pneumonia (LIP). We here report three cases of HTLV-1 carriers showing miliary micro-nodules throughout both lungs. Microscopic examination in the video assisted thoracic surgery biopsies demonstrated that all cases had multiple discrete micro-nodules which consisted of marked lymphoid infiltration, granulomas, eosinophils and a few foci of necrosis inside the granuloma. No findings indicating ATLL, other neoplastic conditions, infection or interstitial pneumonia, including DPB and LIP, were present following panels of special staining and immunohistochemical examinations. Two patients improved without treatment within one month, with no evidence of recurrence after 7 years. One patient showed slow deterioration of lung reticular shadows in spite of a low dose corticosteroid therapy (prednisolone 10 mg/day). We believe these cases may be a newly recognized variant of HABA.
    Pathology International 02/2013; 63(2):108-12. DOI:10.1111/pin.12030 · 1.59 Impact Factor
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    ABSTRACT: We present 3 cases of rapidly progressive interstitial pneumonia (RPIP) associated with clinically amyopathic dermatomyositis (C-ADM) that were treated with two courses of direct hemoperfusion with polymyxin B-immobilized fiber column (PMX-DHP). Despite initial treatment with high-dose corticosteroids, pulsed cyclophosphamide, and cyclosporine, the lung disease and hypoxemia deteriorated in all the patients. After PMX-DHP treatment, the PaO(2)/FiO(2) ratio and serum LDH and KL-6 were improved, the abnormal shadows in chest high-resolution computed tomography (HRCT) scans gradually decreased, and, finally, all patients survived. These findings indicate that PMX-DHP treatment could be effective in the management of RPIP in patients with C-ADM in combination with conventional therapy.
    Modern Rheumatology 10/2012; 24(2). DOI:10.1007/s10165-012-0777-8 · 2.21 Impact Factor
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012

Publication Stats

928 Citations
314.31 Total Impact Points


  • 1996–2015
    • Kumamoto University
      • • Department of Respiratory Medicine
      • • Graduate School of Medical Sciences
      • • School of Medicine
      Kumamoto, Kumamoto, Japan
  • 2008–2011
    • National Hospital Organization Kumamoto Medical Center
      Kumamoto, Kumamoto Prefecture, Japan
  • 1989
    • University of California, San Francisco
      • Cardiovascular Research Institute
      San Francisco, CA, United States