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Background Idiopathic pulmonary fibrosis (IPF) is a fatal fibrotic lung disease with few effective therapeutic options. Recently, drug repositioning, which involves identifying novel therapeutic potentials for existing drugs, has been popularized as a new approach for the development of novel therapeutic reagents. However, this approach has not yet been fully utilized in the field of pulmonary fibrosis. Methods The present study identified novel therapeutic options for pulmonary fibrosis using a systematic computational approach for drug repositioning based on integration of public gene expression signatures of drug and diseases (in silico screening approach). Results Among the top compounds predicted to be therapeutic for IPF by the in silico approach, we selected BI2536, a polo-like kinase (PLK) 1/2 inhibitor, as a candidate for treating pulmonary fibrosis using an in silico analysis. However, BI2536 accelerated mortality and weight loss rate in an experimental mouse model of pulmonary fibrosis. Because immunofluorescence staining revealed that PLK1 expression was dominant in myofibroblasts while PLK2 expression was dominant in lung epithelial cells, we next focused on the anti-fibrotic effect of the selective PLK1 inhibitor GSK461364. Consequently, GSK461364 attenuated pulmonary fibrosis with acceptable mortality and weight loss in mice. Conclusions These findings suggest that targeting PLK1 may be a novel therapeutic approach for pulmonary fibrosis by inhibiting lung fibroblast proliferation without affecting lung epithelial cells. In addition, while in silico screening is useful, it is essential to fully determine the biological activities of candidates by wet-lab validation studies.

Primary pleural melanoma is an extremely rare neoplasm, and to the best of our knowledge, there have been only 8 case reports of this condition in the English literature. We herein report a rare case in which the cytological and immunocytochemical analyses of pleural fluid and ultrasonography (US)-guided biopsy of a pleural lesion were useful for the diagnosis primary pleural melanoma. This case highlights the importance of careful physical examinations, cytomorphologic and immunocytochemical analyses of pleural fluid, as well as the utility of US-guided biopsy of the pleural lesions in the diagnosis of primary pleural melanoma.

Lenvatinib is a multi-targeted tyrosine kinase inhibitor available for the treatment of unresectable hepatocellular carcinoma (HCC). We herein report an 84-year-old-man with interstitial pneumonia caused by lenvatinib. Four months after the start of lenvatinib administration for HCC, chest computed tomography revealed bilateral ground-glass opacity. However, he continued to take lenvatinib for four more months until he complained of dyspnea on exertion. This is a case of lenvatinib-induced interstitial pneumonia that progressed relatively slowly with a long asymptomatic period despite the appearance of pneumonia on image findings.

Background : Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation : A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion : Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients. J. Med. Invest. 67 : 358-361, August, 2020.

Rationale: The in vivo pharmacokinetics analysis provides the valuable information about not only the pharmacological mechanism but also toxicity evaluation. Although nintedanib, one of the approved antifibrotic drug, is widely used to the treatment for idiopathic pulmonary fibrosis, no previous reports have focused on the localization of nintedanib in lung tissue. In this study, we investigated the localization of nintedanib in pulmonary fibrosis using Mass Spectrometry Imaging (MSI) and compared with those of cyclophosphamide. Methods: Pulmonary fibrosis was induced in mice by subcutaneously administration of bleomycin-A5. Lung tissues were collected 2-48 hours after oral administration of nintedanib or cyclophosphamide. The lung tissues were histologically examined and analyzed using an imaging mass spectrometer (iMScope TRIO). Results: The detection intensities of nintedanib were highest in lung tissues collected 4-6 hours after administration of nintedanib. The detectable period of nintedanib was longer than 24 hours. Those of cyclophosphamide diminished earlier than nintedanib. This tendency was same in both fibrotic region and normal region. Conclusions: Nintedanib is distributed in lung tissues regardless of the structural changes by pulmonary fibrosis, and the duration was estimated to be longer than cyclophosphamide. These results also indicate that MSI is a useful technique for evaluating the distribution of antifibrotic drugs in pulmonary fibrosis.

Peripheral T cell lymphoma not otherwise specified (PTCL-NOS) is a rare entity of lymphoma. We herein report an even rarer case of a 68-year-old male with PTCL-NOS presenting as an endobronchial lesion, and review previously published cases in the literature. Initially, he was referred to our hospital for further investigation of the right upper lobe consolidation on chest radiograph. Computed tomography and 18F-fludeoxyglucose positron emission tomography revealed a right hilar mass with obstruction of the main bronchus and submandibular, right axillary and mediastinal lymphadenopathy. Pathological examination of the biopsy specimens from of the endobronchial lesion and subcutaneous nodule revealed PTCL-NOS. Chemotherapy was started but he finally died due to septic shock after the second-line chemotherapy. Keywords: Peripheral T cell lymphoma not otherwise specified, Airway lesion, Transbronchial biopsy

We herein report a case of huge lymphatic and venous malformations of the mediastinum (LVM). A 19-year-old man presented for evaluation of a mediastinal mass. On chest computed tomography, the mass demonstrated contrast enhancement and showed dilated veins draining into the superior and inferior vena cava, with multiple scattered calcifications. The lesion was enhanced heterogeneously on T1-weighted magnetic resonance imaging (MRI) and hyperintense on T2-weighted MRI. Contrast-enhanced MRI revealed that the mass was enhanced, with the multilocular part marginally enhanced. From these images, we diagnosed him with LVM. Given that an operation presented a high risk, we decided to follow him up without any treatment. Keywords: Lymphatic and venous malformations, Vascular tumors, Vascular malformations

We herein report the case of a 37-year-old immunocompetent man who died from Pneumocystis jirovecii pneumonia (PCP). He was initially treated for an acute exacerbation of interstitial pneumonia; however, the elevation of the patient’s serum (1-3) β-D glucan (BG) level suggested the possibility of PCP and sulfamethoxazole trimethoprim was added. A postmortem pathological examination and retrospective Grocott's methenamine silver (GMS) staining of the bronchoalveolar lavage fluid (BALF), which was obtained on the day of admission, revealed PCP. The present case suggests that it is essential to perform a BG assay and GMS staining of BALF specimens when patients show diffuse ground-glass opacity on chest computed tomography, regardless of their immune status.

Background: Recently, it is reported that Actinomyces meyeri is the most common species causing actinomycosis. However, to our knowledge, there was no report about pulmonary actinomycosis attributable to A. meyeri presenting as cardiac tamponade. Case presentation: Hereby we describe a case of pulmonary actinomycosis attributable to A. meyeri presenting as cardiac tamponade. At first, the patient was diagnosed with bacterial pericarditis with lung abscess in the left lower lung lobe and underwent pericardial drainage. Three days after the removal of the drainage tube, atrial fibrillation followed by cardiac arrest with asystole occurred and immediate cardiopulmonary resuscitation restored his circulation. Thereafter, he underwent pneumocentesis of the lung abscess and the culture grew A. meyeri. He was successfully treated with penicillin G. Conclusion: This is the first case of pulmonary actinomycosis attributable to A. meyeri presenting as cardiac tamponade. We believe that an increased awareness of the disease is necessary to expedite diagnosis therefore minimizing morbidity and mortality.