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Objectives To describe the treatment patterns and determine the effectiveness and safety of nivolumab treatment for non-small cell lung cancer (NSCLC) in real-world setting in Japan. Materials and methods Japanese patients with NSCLC who received nivolumab were analyzed retrospectively. Patients who had started nivolumab treatment between April 2016 and December 2016 were enrolled. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness and safety of nivolumab treatment and that of treatments just before and after nivolumab treatment, and programmed death-ligand 1 (PD-L1) expression status, if available, were collected. Factors associated with nivolumab effectiveness identified by univariate and multivariate analyses were further investigated for plotting Kaplan-Meier curves of epidermal growth factor receptor (EGFR) gene mutation status, PD-L1 expression status, and Eastern Cooperative Oncology Group performance status (ECOG PS). Results In this study, 901 NSCLC patients were enrolled. Nivolumab was used the most as a second line treatment with a median number of nivolumab doses of five. The median overall survival (OS) was 14.6 months, one-year survival rate was 54.3 %, and median progression-free survival (PFS) was 2.1 months. The objective response rate was 20.5 % and disease control rate was 57.4 %. According to multivariate analyses, better OS and PFS were associated with favorable ECOG PS and absence of liver metastasis. Better PFS was observed in patients without EGFR mutation and patients with smoking history. PFS and best overall response in PD-L1 expression subgroups were expression level-dependent. The overall incidence of irAEs was 45.8 %, and the incidence of adverse events of grade 3 or higher was 14.0 %. Conclusion The real-world effectiveness and safety of nivolumab is consistent with that reported by previous clinical trials and other real-world data. Subgroup analysis showed that ECOG PS, EGFR mutation status, smoking status, and PD-L1 were associated with the effectiveness of nivolumab.

Objectives We conducted a subanalysis of data from the multicentre, retrospective observational Nivolumab Japan Real World (CA209-9CR) study to evaluate nivolumab effectiveness and safety in elderly patients (aged ≥75 years) with advanced/metastatic non-small cell lung cancer.Materials and methods Medical record data of patients initiating nivolumab treatment between April 2016 and December 2016 were collected using electronic data capture from 23 cancer hospitals in Japan between March 2017 and August 2018. Nivolumab treatment data were collected to investigate the treatment patterns by age group (

Background Spontaneous osteonecrosis of the knee (SONK) is one of the acute knee pain disorders arising in elderly patients. The presence of knee varus alignment and the size of necrotic area have been reported as the negative prognostic factors in prior studies. However, no previous study has yet clarified the radiological analysis of the lower extremity in SONK compared with that in osteoarthritis. The purpose of this study was therefore to identify the radiographic findings of the lower extremity in SONK. Methods Sixty-three knees of Kellgren–Lawrence classification grade 1 or 2 without any trauma treated between April 2012 and March 2014 were enrolled in this study. These knees were divided into two groups according to their magnetic resonance imaging (MRI) findings: SONK group (31 knees) and OA group (32 knees). Using a long leg standing X-ray, femorotibial angle (FTA), mechanical axis deviation (MAD), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA) and joint line convergent angle (JLCA) were compared between groups. Correlation between each parameter and the width ratio (WR) of the necrotic lesion were analyzed. Results FTA, MAD, MPTA and JLCA showed significant differences between the SONK and OA groups. In the SONK group, FTA was positively correlated with WR, and, MAD and MPTA was negatively correlated with WR. Conclusions Compared with OA, SONK is associated with a significantly larger varus deformity at the proximal tibia, and larger joint play in the coronal plane.

Background Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic pattern of acute lung involvement with intra-alveolar fibrin deposition. However, the clinical significance of the pathological findings of AFOP remains unclear. This study aimed to explore the clinical significance of AFOP through a comprehensive clinical examination. Methods The medical records of patients with lung diseases accompanied by the pathological finding of intra-alveolar organization between January 2010 and December 2019 were retrospectively reviewed. The clinical and radiological findings were compared between the groups with and without the histologic pattern of AFOP. Results We identified 34 patients with AFOP (AFOP group) and 143 without AFOP (non-AFOP group). The underlying diseases of the AFOP group were as follows: 19 patients had cryptogenic organizing pneumonia (OP), 5 had connective tissue diseases, 3 had radiation pneumonitis, 3 had chronic eosinophilic pneumonia, 2 had myelodysplastic syndromes, and 2 had drug-induced pneumonia. Fever was more common, the time from symptom onset to biopsy was shorter, and the serum C-reactive protein level was higher in the AFOP group than in the non-AFOP group. On high-resolution computed tomography, 85% of patients had OP pattern, and halo sign was more common in the AFOP group. Corticosteroids were effective in 94% of the patients in the AFOP group; however, recurrences were more frequent, and a higher corticosteroid dose was needed during recurrence. Conclusions AFOP might be an early phase of a histologic pattern associated with known etiologies. In addition, it could be a marker indicating intense inflammatory diseases with a tendency of recurrence.

Background: Bronchial occlusion therapy using silicon spigots is effective for intractable pneumothorax. However, sometimes the pneumothorax is refractory to bronchial occlusion because of collateral ventilation. For such difficult pneumothoraces, we attempted an intrabronchial infusion of autologous blood plus thrombin to control collateral ventilation and stop air leaks. Methods: We performed bronchial occlusions using silicon spigots in patients with spontaneous pneumothorax secondary to emphysema and refractory to chest drainage, but which was inoperable owing to each patient’s poor surgical candidacy and poor overall health condition. When bronchial occlusion proved ineffective, we undertook intrabronchial infusion of autologous blood plus thrombin, 2 to 4 days after bronchial occlusion. A catheter was inserted into the subpleural area, through a gap between the silicon spigot and the bronchial wall, using a flexible bronchoscope under fluoroscopic guidance. Autologous blood, followed by a thrombin solution, was infused using the catheter. We repeated the same infusion a total of 4 to 6 times while changing the target bronchi. All interventions were performed under local anesthesia. Results: The subjects were 9 men, aged from 61 to 88 years, with smoking histories. Three patients also had interstitial pneumonia, and 6 patients had undergone pleurodesis in vain before bronchial occlusion. For 4of the 9 patients, autologous blood plus thrombin infusions successfully stopped air leaks, and in 3 patients, intrabronchial infusions and pleurodesis halted leaks altogether. Conclusion: Intrabronchial infusion of autologous blood plus thrombin was effective for intractable pneumothoraces that could not be clinically managed, even by bronchial occlusion using silicon spigots.

To explore the implications of the structure/ function relationships in factor XIII. a patient with severe A subunit deficiency was examined at the DNA and RNA levels. Nucleotide sequence analysis of the patient's DNA amplified by PCR revealed that the patient had a replacement of C by T in the codon for Arg260. RT-PCR analysis demonstrated that only one kind of mRNA coding for the Arg260-Cys mutation was expressed in the patient at a normal level. Another possible defective allele of the A subunit gene with a G-A polymorphism was not expressed (null allele). The substitution of Arg260 by Cys located on the interface of two A subunits would preclude the reciprocal ionic interaction (salt bridge) between Arg260 and Asp404. Molecular modelling and, for the first time, molecular mechanics calculated that Cys260 changed the local conformation of the A subunit and reduced the electrostatic interaction between two monomers, suggesting destabilization of the molecule's dimer.

Culture positivity of percutaneous aspiration material" is not included in the current bacteriological criteria for diagnosis of pulmonary nontuberculous mycobacterial (NTM) diseases, which were published by the Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) in 2007 or those released by the Japanese Society for Tuberculosis in 2008. However, percutaneous aspiration is a reliable technique for the detection of causative microorganisms isolated from the focus of infection. We discuss the benefits of including positive culture of percutaneous aspiration material in the bacteriological diagnostic criteria of pulmonary NTM diseases.We reviewed the radiological images and clinical courses of pulmonary diseases in which NTM cultures were obtained from percutaneously aspirated materials at our hospital from 1991 to 2011. Aspiration was carried out under local anesthesia, usually with fluoroscopic guidance. After percutaneous insertion of a 22-gauge needle attached to a 20-mL syringe containing about 3 mL of saline, the lesion specimen was withdrawn together with the saline. After the needle was pulled out, the aspirated material and saline were transferred to test tubes for cytological and microbiological examinations. In patients with thin-walled cavitary lesions, saline was injected into the cavity and then aspirated.Percutaneous aspiration was performed in 2,742 patients and NTM disease was detected in 51 patients. Of these 51 patients, 12 had solitary nodular lesions, and in many of these patients, no NTM bacilli could be detected in the sputa or bronchial washing specimens. Mycobacterium avium was identified in 10 of the 12 cases. Four of these 10 patients were followed up after their diagnosis without any treatment: 3 showed spontaneous reduction in lesion size, while 1 patient's condition remained unchanged. Four of the remaining 6 cases were treated with anti-NTM medications, and lesion size reduced in 2 cases, while no change or deterioration was seen in the other 2. Aspiration from solitary small cavitary lesions showed a relatively high number of NTM colonies. Pneumothorax was the only complication of the aspiration procedure.If the diagnostic criteria for pulmonary NTM diseases include positive culture in percutaneous aspiration material, the diagnosis of solitary nodular NTM lesions would become easier; at present, these lesions are often diagnosed only upon surgical resection. Further, clinical studies on the possibility of spontaneous shrinkage of the solitary lesion and the value of its medical treatment would be promoted. Aspiration can easily differentiate NTM disease from pulmonary abscess or fungal infection in patients with a solitary lesion or small cavity.

Our aim was to assess computed tomography (CT) features of Mycobacterium kansasii pulmonary infection (M. kansasii infection). A total of 29 cases confirmed to have M. kansasii infections were analyzed. The main locations of pulmonary changes, incidence, and various imaging features of the cavity (location, maximum diameter, wall thickness, satellite nodules, intracavitary fluid), and other imaging findings such as nodules, consolidation, and bronchiectasis, were visually assessed on CT images. Locations of the main abnormalities were as follows: right S2 41%; right S1 31%; left S1+S2 2: 21%. A total of 49 cavities were observed in 24 (83%) cases. The mean maximum diameter, wall thickness, and ratio of wall thickness to the maximum diameter were 33.0 mm, 4.7 mm, and 0.19, respectively. Shapes of the cavities were round in nine (18.4%), oval in 17 (34.7%), and tubular/meandering in 23 (47%). Satellite nodules were found in only 30.6% of patients (n = 15). Small nodules were found in 26 (89.7%) patients, and most of them showed a centrilobular distribution. The characteristic CT findings suggestive of M. kansasii infection include cavities located in the right posterior or apical segment with a tubular/meandering shape and a thin wall.

A 27-year-old woman who had been treated for pulmonary tuberculosis with anti-tuberculosis drugs for three months was admitted to our hospital because of pain in the chest and back. Chest CT showed improvement in the pulmonary tuberculosis lesions in the right middle lobe and S8, but there was a large pleural mass in the right lower lung field. Histopathological findings of the percutaneous biopsy showed epithelioid cell granulomas that were negative for acid-fast bacilli. We diagnosed the mass as pleural tuberculoma with intrapulmonary invasion. The pleural tuberculoma improved without any additional therapy.

CASE 1: A 74-year-old man having a week's fever and diagnosed with a liver abscess was treated with several antibiotics and percutaneous liver drainage. His respiration gradually worsened and chest computed tomography (CT) showed right pleural effusion and a left-lung mass. Percutaneous fine needle aspiration of the pulmonary mass detected Entamoeba histolytica. CASE 2: A 44-year old, zoo office worker admitted for fever and right chest pain was found in CT to have right pleural effusion and a mass with a liver abscess necessitating abscess drainage. Injected contrast medium detected a fistula connected to the right. Following surgical drainage, E. histolytica was detected from the resected lung. Both cases responded well to metronidazole.

We encountered two cases of systemic arterial supply to the basal segments of bilateral lung with elevated serum CEA levels. The patients were a 36-year-old man and a 30-year-old man with the abnormal chest shadows, discovered during physical checkups. A chest computed tomogram (CT) of the 36-year-old patient showed reticulonodular shadows in the bilateral lower lobe with anomalous vessels arising from the descending aorta and running into the lower lobe on each side, and his abdominal CT revealed a duplicated vena cava inferior. His aortogram confirmed an anomalous systemic arterial supply to the basal segments of bilateral lungs. The chest CT of the 30-year-old patient revealed a cystic lesion in the right lower lobe and no abnormality in the left lung field. His aortograms showed aberrant systemic arterial supplies to the bilateral lower lobe. Because the cystic lesion had increased in size, it was resected and an anomalous systemic artery was seen. Intralobar sequestration in the right lung and anomalous systemic arterial supply in the left lung was diagnosed. Serum CEA was high at the initial visit in each patient but it decreased spontaneously in the first patient, and after the resection of the cystic lesion in the second patient. We report two cases of anomalous systemic arterial supply to the basal segments of bilateral lung, which is extremely rare. Our literature search revealed that only 13 cases have been reported to date.

We conducted a retrospective analysis of 7 cases of diffuse alveolar hemorrhage at our hospital, diagnosis of which was made on the presence of bloody bronchoalveolar lavage fluid. There were 3 men and 4 women, with a mean age of 68 years. A rapidly progressiving diffuse infiltrative shadow on chest X-ray film and failing to respond to antibiotic therapy were the major signs of the condition in these cases. Respiratory failure was seen in all cases. In addition to high-dose steroid therapy and mechanical ventilation, we immediately performed plasma exchange. All of the 3 MPO-ANCA-positive patients survived, but 3 of the 4 MPO-ANCA-negative patients died. Diffuse alveolar hemorrhage secondary to ANCA-associated vasculitis usually advances rapidly and its prognosis tends to be poor. However, early initiation of plasma exchange can be expected to improve the survival rate of patients with this disease.

We reported the clinical features of 4 cases with pulmonary Langerhans' cell histiocytosis. All of them were men who had a history of smoking. They ranged in age from 23 to 46 years. Cases 1 and 3 did not stop smoking, while Cases 2 and 4 did stop smoking. All of the chest CTs revealed small nodules and cysts, and during the follow-up period of 8 to 13 years, the numbers of nodules decreased and the walls of the cysts became thin in all of the cases. Their pulmonary function tests revealed restrictive impairment in 3 cases and reduced diffusion capacity in 2 cases, but none showed obstructive impairment. FEV1% and DL(CO) deteriorated during the follow-up period. Case 1 died of respiratory failure after 8 years. Cases 2 and 4 were both alive with home oxygen therapy after 11 and 12 years, respectively. Case 3 was alive but complained of dyspnea on exertion after 13 years. In conclusion, all of the 4 cases showed deterioration of pulmonary function, and one of them died due to respiratory failure. The prognosis of patients with pulmonary Langerhans' cell histiocytosis appears to be poor.

A 77-year-old man underwent radiotherapy for the squamous cell carcinoma of the right lung. Two months after the 60Gy/30fr irradiation was completed, he complained of dyspnea and his chest X-ray showed ground glass opacities and reticular shadows in both lung fields. Severe radiation pneumonitis was diagnosed. Two grams of methylprednisolone did not improve his symptoms and on the next day his hypoxemia worsened. We then tried plasma exchange because of his critical status. His respiratory status improved rapidly after plasma exchange and his chest X-ray showed remarkable improvement 10 days later. We think this case suggests the effectiveness of plasma exchange for severe radiation pneumonitis.

An 80-year-old woman suffered from fever and loss of appetite. Her chest X-ray showed mediastinal tumors and diffuse granular shadows in the bilateral lung fields. Elevations of sIL-2r and M-protein were present. HRCT showed numerous small granules in both lungs and mediastinal lymph node enlargement. Tuberculosis DNA was detected by PCR in her sputum. Later, Mycobacterium tuberculosis was cultured from her sputum. After she started anti-tuberculosis therapy, her general fatigue and elevation of sIL-2r improved gradually. Her chest X-ray revealed a decrease in the size of mediastinal lymph nodes and small granules.

A 23-year-old man had been treated for repeated pneumonia from the age of 16. After a diagnosis of eosinophilic pneumonia at the age of 17, he had been given antibiotics and steroids. At the age of 23, he was referred to our hospital. Although he improved rapidly in response to antibiotic medication, his chest X-ray shadows did not improve. Video-assisted thoracoscopic lung biopsy was performed. Fibrosis and invasion of inflammatory cells were seen on the air duct walls and foreign bodies that were thought to be food residue were detected. A diagnosis of chronic aspiration pneumonia was made pathologically. A brain stem tumor was detected on his brain magnetic resonance imaging, which was thought to be the cause of his mis-swallowing.

A 56-year-old man and a 53-year-old woman with cough, sputum and dyspnea were admitted in the summer. High-resolution computed tomographic findings of the chest showed centrilobular branching opacities like diffuse panbronchiolitis with ground glass opacities. Both cases showed hypoxia, a high titer of serum anti-Tricosporon antibody and exacerbation in their own homes. Video-assisted thoracoscopic lung biopsy revealed granuloma in the bronchioles area. We diagnosed summer type hypersensitivity pneumonitis and this condition improved in response to antigen isolation and steroids. Remarkable changes in the bronchioles were characteristic in the two cases.

A 74-year-old man had been given a diagnosis of myelodysplastic syndrome (MDS), and had been treated with granulocyte-colony stimulating factor (G-CSF). 1 year later, he suffered from fever and his chest X-ray lung biopsy did not provide a diagnosis, video-assisted thoracoscopic lung biopsy was performed, which yielded a histological diagnosis of organizing pneumonia. His pulmonary disease was diagnosed as secondary organizing pneumonia due to MDS, and was treated successfully with steroids. Vigorous efforts to establish a histological diagnosis is needed for the antibiotics-resistant pneumonia in the case of MDS.

An infiltrative shadow was observed in the upper lobe of the left of a 60-year-old man lung during the course of paroxysmal tachycardia. Fever and coughing occurred one month later, and ground-glass opacities (GGOs) were found extensively in the lower left lung field. Although his condition strongly suggested allergic bronchopulmonary aspergillosis (ABPA) due to significantly increased eosinophil count in the peripheral blood and bronchoalveolar lavage fluid of the lower lobe of the left lung, anti-aspergillus antibody precipitation, and positive immediate intradermal test, the Rosenberg diagnostic criteria for ABPA were not satisfied. He was given a diagnosis of eosinophilic pneumonia, and GGO disappeared when itraconazole and prednisolone were administered. However, since the shadow in the upper lobe of the left lung later increased and percutaneous thoracocentesis revealed the presence of Aspergillus fumigatus, prednisolone treatment was discontinued and micafungin was administered. Nonetheless, the shadow spread into both lungs and regardless of treatment with amphotericin-B, the patient died. Although the present case is different from a typical ABPA, it indicates that allergic reaction can be induced by Aspergillus infection in the lung field, apart from the central airway. In addition, the development of an appropriate therapeutic strategy against both infection and allergy in such cases is essential.