Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/µL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.

[A Patient with Recurrent Invasive Thymoma Obtaining Long-Term Survival by Chemotherapy with Amrubicin Alone as the Third Treatment].

The patient was a 68-year-old woman. She was diagnosed with invasive thymoma 12years prior and underwent chemoradiotherapy( adriamycin, cisplatin, vincristine, and cyclophosphamide: ADOC)plus radiation exposure(62G y). After 11 years, the disease relapsed. Carboplatin plus paclitaxel(CP)therapy as a second-line therapy was ineffective, leading to enlargement of the primary tumor and the development of pleurisy. The third-line treatment with a single dose of amrubicin resulted in good disease control. There were no serious adverse events, and the drug tolerance was good. The patient has undergone 21courses of this treatment as of the time of this report and continues to maintain complete response(CR). No chemotherapy regimen as more than a second-line therapy demonstrated efficacy against recurrent thymoma. Amrubicin monotherapy may be an effective treatment option that may result in long-term survival with minor side effects.

[A Case in Which Toxic Epidermal Necrosis Developed during Treatment with the Immune Checkpoint Inhibitor Pembrolizumab for Recurrent Patients Following Lung Cancer Surgery].

The patient was a 66-year-old male. Following surgery for pulmonary adenocarcinoma in the upper right lobe and adjuvant chemotherapy, the patient relapsed. We carried out treatment using the immune checkpoint inhibitor pembrolizumab (KEYTRUDA®)for high expression of PD-L1. Following the first administration, severe drug eruption occurred and despite temporary improvement seen by intravenous infusion of steroids in combination with oral administration and external use thereof, it relapsed in the early stages and toxic epidermal necrosis developed. Skin problems were improved by multidisciplinary treatments such as gammaglobulin therapy, systemic steroid administration, and broad-spectrum antibiotics. There were no reports oftoxic epidermal necrosis occurring during pembrolizumab administration for lung cancer. This case went through a unique course in which the disease relapsed into a more severe condition at an early stage following temporary remission.

[A Case in Which Good Control of Carcinomatous Serositis Was Achieved Using Chemotherapy Including Albumin-Bound Paclitaxel(Nab-PTX)for Advanced-Stage Pulmonary Adenocarcinoma Exhibiting Carcinomatous Pleurisy and Carcinomatous Pericarditis].

The subject was a 63-year-old man. The patient was transported by ambulance to the hospital because of dyspnea caused by carcinomatous pleurisy and carcinomatous pericarditis, after which pericardial drainage was performed; however, Staphylococcus aureus bacteremia arose as a complication. Adequate control of carcinomatous serositis was achieved usingchemotherapy, includingalbumin -bound paclitaxel(nab-PTX), which is a nanoparticle formulation bindinghuman serum albumin and paclitaxel, in combination with 1 course of antibiotics. For cancerous serositis cases, platinum combination chemotherapy usingnab -PTX is believed to be 1 treatment option in which good disease control can be expected along with bevacizumab, whose efficacy has already been confirmed.

Immunoglobulin G4-related lung disease: clinicoradiological and pathological features.

BACKGROUND AND OBJECTIVE: Immunoglobulin G4 (IgG4)-related disease is a multi-organ disorder that can include the lungs. IgG4-related lung disease can present in various forms; the clinical, radiological and pathological features of patients with this disease have been assessed. METHODS: Forty-eight patients suspected of having IgG4-related lung disease, with a high serum concentration of IgG4 and abundant IgG4-positive plasma cell infiltration into the intrathoracic organs, were retrospectively evaluated. Their clinical features, chest imaging findings and pathological findings were examined, with final diagnoses made by an open panel conference. RESULTS: Of the 48 patients, 18 with extrathoracic manifestations were diagnosed as having IgG4-related lung disease. Most of these patients were middle-aged to elderly men. IgG4-related lung disease was characterized by high serum concentrations of IgG and IgG4, normal white blood cell count and serum C-reactive protein concentration and a good response to corticosteroids. Common radiological findings included mediastinal lymphadenopathy and thickening of the perilymphatic interstitium, with or without subpleural and/or peribronchovascular consolidation. Pathological examination showed massive lymphoplasmacytic infiltration with fibrosis in and around the lymphatic routes, with distribution well correlated with radiological manifestations. CONCLUSIONS: The findings suggest that the intrathoracic manifestations of IgG4-related lung disease develop through lymphatic routes of the lungs and show various clinical characteristics. Because some lymphoproliferative disorders show similar findings, the correlation of clinicoradiological and pathological characteristics is crucial for the diagnosis of IgG4-related lung disease.

Cell behavior analysis to evaluate proliferative potentials of human lymphocytes expanded and activated for therapeutic use.

The cluster designation 3-lymphokine activated killer (CD3-LAK) culture was conducted using human lymphocytes obtained from different donors. It was found that donor-dependent variances existed in terms of lag time and minimum doubling time, which were process parameters for comprehending the proliferative potentials of cells in an early phase with weak growth and in a subsequent phase with active growth, respectively. To correlate these variances with culture performances, cellular behaviors were estimated by constructing a custom-made observation tool that can capture and process images of culture surfaces. The tool enabled us to determine time-lapse changes in an average projected cell area and the frequency of cell aggregates during the culture in a noninvasive manner. It was found that linear relationships were obtained both between lag time and average projected cell area, and between minimum doubling time and formation rate of cell aggregates, irrespective of culture performance fluctuation depending on each donor state. It is concluded that the developed tool is helpful for operating CD3-LAK culture while monitoring the state of human lymphocytes.

Relations between individual cellular motions and proliferative potentials in successive cultures of human keratinocytes.

In the successive cultures of human keratinocyte cells, cellular motions of extension and rotation were analyzed based on observation of the individual cells, to evaluate the proliferative potential in a whole cell population. In lag phases of the serial cultures, an extension index of individual cells, R(E), was defined as an average spreading rate divided by initial cell area for each cell. The mean value of R(E) was found to relate to prolongation of lag time; namely it decreased with increasing passage number in the successive cultures approaching cellular senescence. During the courses of the cultures, the rotation rate of paired cells was also measured through time-lapse observation. The mean value of rotation rate, [Formula: see text], decreased with an increase in doubling time caused by the progress of cellular age, reaching an almost constant value of [Formula: see text] h(-1) in the cultures with prolonged doubling time of over 59 h. It was concluded that the indices determined from the motions of individual cells, R(E) and [Formula: see text], were correlated with the lag time and doubling time, respectively, which are growth parameters varied with the vitality of the cells approaching cellular senescence.

Dendrimer-immobilized culture surface as a tool to evaluate formation of cellular cytoskeleton of anchorage-dependent cells.

Anchorage-dependent cultivation of human epithelial and keratinocyte cells was carried out on surfaces modified with synthesized dendrimers. Notable elongation of the epithelial cells was recognized on the culture surface immobilized with a dendrimer having D-glucose as a functional ligand, but not when a dendrimer having L-glucose was used or when the dendrimer was ligand-free. This morphological change was attributable to a temporary grasping of the cells at the D-glucose moiety via a glucose transporter-mediated mechanism present in the cell membrane. Following visualization of the actin filaments of the cells, it was considered that the cellular elongation on the D-glucose-bound dendrimer surface reflected the degree of formation of the cellular cytoskeleton. The cellular roundness was calculated by means of image analysis of the individual cells and employed as a parameter to evaluate the formation of the cellular cytoskeleton. In the culture of keratinocytes on the D-glucose-bound dendrimer surface, it was demonstrated that the decrease in the ratio of elongated cells (i.e., cells with a low roundness value) was correlated with the deterioration in the growth potential associated with cellular senescence.