Background The early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI (18F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC).Methods Twenty-five patients with previously treated NSCLC were enrolled prospectively and underwent 18F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy.Results The disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADCmean (ie, negative ΔADCmean) and lower ΔTLG+ΔADCmean than patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADCmean had the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADCmean value <16.5 was significantly associated with longer median progression-free survival (9.0 vs 1.8 months, p<0.00001) and overall survival (23.6 vs 4.7 months, p=0.0001) compared with ΔTLG+ΔADCmean value ≥16.5. A multivariate Cox model revealed that ≥16.5 ΔTLG+ΔADCmean was an independent predictor of shorter progression-free survival (HR 37.7) and overall survival (HR 9.29).Conclusions A combination of ΔTLG and ΔADCmean measured by integrated 18F-FDG PET/MRI may have value as a predictor of the response and survival of patients with NSCLC following nivolumab therapy.Trial registration number UMIN 000020707.

Although hematological toxicities (HT) are the leading adverse events of systemic chemotherapy, the estimation of severe HT is challenging. Recently, 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) accumulation with PET has been considered a biomarker of the cell proliferation. This study aims to elucidate whether the vertebral accumulation of 18F-FLT could estimate severe HT during platinum-doublet chemotherapy.

The presence of malignant pleural effusion (MPE) frequently indicates locally advanced non-small cell lung cancer (NSCLC). The conventional management of MPE involves pleurodesis using a sclerosant substance. The Perng et al. reported injection into chest cavity using paclitaxel for 18 MPE cases. In this report overall response rate was 92.9%. No disease progression was noted among evaluable patients. Therefore we focused on Paclitaxel which had antitumor effect and a pleural effusion control, and planned clinical trials phase I and II for the treatment of MPE. The primary objective of this study was to evaluate the efficacy of paclitaxel pleurodesis, the side effects and systemic antitumor effect. Patients were enrolled cytologically proven malignant pleural effusion of NSCLC. Radiotherapy and systemic chemotherapy were also not allowed within 4 weeks. After adequate drainage and assurance of lung re-expansion, paclitaxel diluted in normal saline was infused through a double lumen catheter. The starting dose was 100 mg/m2 with dose escalation schedule of 125, 150, and 175mg/m2. The catheter was clamped for 24 hrs. Chest drainage was continued until daily drainage was under 200 ml, and the tube was removed. To measure paclitaxel concentration, serum and pleural fluid samples were collected 0.5, 1, 3, 6, 24, 72hrs after the end of drug instillation. The treatment response of malignant effusion was evaluated according to the following criteria: complete response (CR), no fluid reaccumulation for at least 4 weeks as determined by CT scan; partial response (PR), recurrence of effusion to less than 50% of the original effusion volume within 4 weeks after treatment; failure, recurrence of effusion greater than 50% of the original volume, patients were symptomatic and need for thoracentesis to relieve symptoms within 4 weeks. The criteria for main tumor lesion response to intrapleural paclitaxel treatment were in accordance with Response Evaluation Criteria in Solid Tumors (Revised RECIST guideline version 1.1). From April 2009 to November 2012, 12 patients were enrolled. There were minimal local and systemic toxicities. The serum level of PXL of the cases with the effect of treatment was significantly higher than these of the cases without the effect. Over all response rate was 67%. No disease progression was noted among evaluable patients. We decided to plan a late phase II study of the therapy with 175 mg/m2, because it was not dosage-dependent even if it was a low dose and serum level-dependent.

Background:Nanoparticle albumin-bound paclitaxel (nab-PTX), which avoids toxicities associated with a vehicle used in solvent-based PTX, has already shown safety and efficacy in patients with non-small cell lung cancer (NSCLC).Methods:A phase II study was performed to assess the safety and efficacy of nab-PTX monotherapy as second-line chemotherapy after cytotoxic anticancer drugs for previously treated advanced NSCLC. Thirty-two patients with advanced NSCLC who had previously undergone 1 regimen of cytotoxic anticancer drugs were enrolled. Nab-PTX was administered intravenously at a dose of 100mg/m(2) on days 1, 8, and 15 of a 28-day cycle. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity profile were evaluated.Results:The ORR was 28.1%, the DCR was 71.9%, median PFS was 3.9 months (95% confidence interval [CI] 2.7-5.1 months), and median OS was 10.9 months (95% CI 9.5-12.3 months). The mean relative dose intensity of nab-PTX was 77%. Grade 3 or 4 neutropenia, and grade 3 febrile neutropenia were observed in 11 and 1 of 32 patients, respectively. As nonhematologic toxicities, grade 3 peripheral sensory neuropathy and pneumonitis were each observed in 2 of 32 patients.Conclusion:Nab-PTX is an active and well-tolerated regimen in patients with previously treated NSCLC.

The Journal of DermatologyVolume 44, Issue 5 p. e87-e88 Letter to the Editor Erythema induratum of Bazin which occurred after tumor necrosis factor antagonist therapy Natsuki Baba, Corresponding Author Natsuki Baba bbnatsu@u-fukui.ac.jp Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanCorrespondence: Natsuki Baba, M.D., Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. Email: bbnatsu@u-fukui.ac.jpSearch for more papers by this authorWataru Takashima, Wataru Takashima Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this authorAtsushi Tokuriki, Atsushi Tokuriki Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this authorShingo Ameshima, Shingo Ameshima Department of Respiratory Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this authorMinoru Hasegawa, Minoru Hasegawa Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this author Natsuki Baba, Corresponding Author Natsuki Baba bbnatsu@u-fukui.ac.jp Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanCorrespondence: Natsuki Baba, M.D., Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan. Email: bbnatsu@u-fukui.ac.jpSearch for more papers by this authorWataru Takashima, Wataru Takashima Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this authorAtsushi Tokuriki, Atsushi Tokuriki Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this authorShingo Ameshima, Shingo Ameshima Department of Respiratory Medicine, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this authorMinoru Hasegawa, Minoru Hasegawa Department of Dermatology, Division of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, JapanSearch for more papers by this author First published: 20 January 2017 https://doi.org/10.1111/1346-8138.13716Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume44, Issue5Special Issue: Dermoscopy enhances insight into correct diagnosis (pages 489–551)May 2017Pages e87-e88 RelatedInformation

Osteogenesis Imperfecta Associated with Dendriform Pulmonary Ossification Miwa Morikawa, Yuh Fukuda, Yasuhiro Terasaki, Harumi Itoh, Yoshiki Demura, Masato Sasaki, Yoshiaki Imamura, Chisato Honjo, Yukihiro Umeda, Masaki Anzai, Shingo Ameshima, Takeshi Ishizaki, and Tamotsu Ishizuka Third Department of Internal Medicine and Department of Radiology, University of Fukui Faculty of Medical Sciences, Fukui, Japan; Department of Diagnostic Pathology, Itabashi Chuo Medical Center, Tokyo, Japan; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan; Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan; Division of Thoracic Surgery and Division of Surgical Pathology, University of Fukui Hospital, Fukui, Japan; and Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan

A 62-year-old man was admitted to our hospital because of wheezing and dyspnea. Chest computed tomography showed ground-glass opacity and some centrilobular nodules. Chronic eosinophilic pneumonia complicated with Mycoplasma pneumoniae infection was diagnosed on the basis of bronchoalveolar lavage eosinophilia and blood findings. However, based on the clinical course, the patient was suspected to have eosinophilic bronchiolitis. This case suggests the possibility that eosinophilic inflammation can occur concomitantly in the central airway and distal airway.

The aim of this prospective study was to clarify whether dual-timepoint F-18-FDG PET imaging results are useful to predict long-term survival of idiopathic pulmonary fibrosis (IPF) patients. Methods: Fifty IPF patients underwent F-18-FDG PET examinations at 2 time points: 60 min (early imaging) and 180 min (delayed imaging) after F-18-FDG injection. The standardized uptake value (SUV) at each point and retention index value (RI-SUV) calculated from those were evaluated, and then the results were compared with overall and progressionfree survival. Results: A multivariate Cox proportional hazards model showed higher RI-SUV and higher extent of fibrosis score as independent predictors of shorter progression-free survival. The median progression-free survival for patients with negative RI-SUV was better than that for those with positive RI-SUV (27.9 vs. 13.3 mo, P = 0.0002). On the other hand, multivariate Cox analysis showed higher RI-SUV and lower forced vital capacity to be independent predictors of shorter overall survival. The 5-y survival rate for patients with negative RI-SUV was better than that for those with positive RI-SUV (76.8% vs. 14.3%, P = 0.00001). In addition, a univariate Cox model showed that positive RI-SUV as a binary variable was a significant indicator of mortality (hazard ratio, 7.31; 95% confidence interval, 2.64-20.3; P = 0.0001). Conclusion: Our results demonstrate that positive RI-SUV is strongly predictive of earlier deterioration of pulmonary function and higher mortality in patients with IPF.

A case of pulmonary tuberculosis with tuberculous tenosynovitis of a finger Hiroyuki Sakai, Masaki Anzai, Maiko Kadowaki, Yukihiro Umeda, Shingo Ameshima and Tamotsu Ishizuka Division of Respiratory Medicine, University of Fukui Hospital A 27-year-old woman was referred to our hospital because of right index finger swelling and an abnormal chest shadow. Although synovial biopsy of the right index finger showed epithelioid granuloma, we did not detect tubercle bacillus from respiratory materials such as sputa and bronchial lavage fluid. Chest CT image and the positive result of QuantiFERON strongly suggested pulmonary tuberculosis with tuberculous tenosynovitis of the finger. We started the standard chemotherapy for tuberculosis under the clinical diagnosis. Fortunately, Mycobacterium tuberculosis was cultured from gastric juice we had obtained before starting the chemotherapy. The right index finger swelling and abnormal chest shadows were significantly improved by the combination of chemotherapy and surgical resection of the synovial lesion. Although tuberculous tenosynovitis is a rare disease, we need to suspect this disease when we observe the swelling of the finger that slowly progresses and try to explore pulmonary tuberculosis. 412

Background Losing the sense of smell, which suggests eosinophilic rhinosinusitis, is a subjective symptom, sometimes reported in asthmatic patients taking controller medication. Upper abdominal symptoms, suggesting gastroesophageal reflux disease (GERD) or functional dyspepsia, occur also in these patients. However, the relationship between these symptoms, concomitant with asthma, and the intensity of eosinophilic airway inflammation remains obscure. Objective To assess the symptoms of asthma and rhinosinusitis, and to examine the relationship between the symptoms and bronchial inflammation, a new questionnaire, the G scale, was developed. To investigate the effects of GERD, dyspepsia, and rhinosinusitis on asthma symptoms and bronchial inflammation, the symptoms of asthma and rhinosinusitis obtained by the G scale, upper abdominal symptoms obtained by the modified F scale, a questionnaire for GERD and dyspepsia, and fractional exhaled nitric oxide (FeNO) were analyzed. Methods A prospective, observational study was performed in four hospitals in Gunma prefecture, and a retrospective analysis was done using data obtained from five hospitals in Gunma prefecture and Fukui prefecture, Japan. A total of 252 patients diagnosed as having asthma participated in the prospective study. Results The frequency of daytime phlegm or losing the sense of smell had a positive correlation with FeNO levels in asthmatic patients taking controller medication. Upper abdominal symptoms, as well as symptoms suggesting rhinitis, were well correlated with asthma symptoms. However, neither upper abdominal symptoms nor rhinitis symptoms increased FeNO levels, which reflect eosinophilic airway inflammation during treatment for asthma. On the other hand, the degree of upper abdominal symptoms or dyspepsia symptoms had a weak but significant negative correlation with FeNO levels. Conclusion Daytime phlegm and losing the sense of smell suggest that eosinophilic airway inflammation persists, despite anti-inflammatory therapy, in patients with asthma. Although rhinitis and GERD made the subjective symptoms of asthma worse, they did not seem to enhance eosinophilic airway inflammation.

ObjectivesRecent advances in endobronchial ultrasonography with a guide sheath (EBUS-GS) have enabled better visualization of distal airways, while virtual bronchoscopic navigation (VBN) has been shown useful as a guide to navigate the bronchoscope. However, indications for utilizing VBN and EBUS-GS are not always clear. To clarify indications for a bronchoscopic examination using VBN and EBUS-GS, we evaluated factors that predict the diagnostic yield of a transbronchial biopsy (TBB) procedure for peripheral lung cancer (PLC) lesions.MethodsWe retrospectively reviewed the charts of 194 patients with 201 PLC lesions (≤3cm mean diameter), and analyzed the association of diagnostic yield of TBB with [18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography and chest computed tomography (CT) findings.ResultsThe diagnostic yield of TBB using VBN and EBUS-GS was 66.7%. High maximum standardized uptake value (SUVmax), positive bronchus sign, and ground-glass opacity component shown on CT were all significant predictors of diagnostic yield, while multivariate analysis showed only high 18F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign as significant predictors. Diagnostic yield was higher for PLC lesions with high 18F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign (84.6%) than for those with SUVmax <2.8 and negative bronchus sign (33.3%). High 18F-FDG uptake was also correlated with tumor invasiveness.ConclusionsHigh 18F-FDG uptake predicted the diagnostic yield of TBB using VBN and EBUS-GS for PLC lesions. 18F-FDG uptake and bronchus sign may indicate for the accurate application of bronchoscopy with those modalities for diagnosing PLC.

Background; Recent studies have reported the effectiveness of magnetic resonance imaging (MRI) for diagnosing pulmonary nodules. However, its utility for cases of diffuse lung injury remains unknown. Purpose; We evaluated the effectiveness of MRI for detecting diffuse lung injury in experimental animals. Methods; Studies were performed with 18 healthy male rats, which were divided into 3 groups; no experimental intervention (control group, n=6), pulmonary edema induced by ligation of the inferior vena cava and intravenous injection of 20% body-weight Ringer’s solution after anaesthesia (ED group, n=6), and interstitial pneumonitis induced by bleomycin (IP group, n=6). After euthanasia, the lungs were inflated by use of a tracheotomy to a pressure of 20 cm H 2 O then excised en bloc. Each specimen was placed in a plastic tube then examined by MRI, with T1 and T2 values acquired by analyzing the obtained images. Results; There was clear visualization provided by the MR images of the lung vascular system, bronchi, and parenchyma in all groups. In the ED and IP groups, increases in diffuse signals from the lung parenchyma were noted, while no such findings were observed in the control group. T1 and T2 values in the ED and IP groups were significantly increased as compared with the control (P

Objective: The aim of this study is to assess the effect of Rho-kinase inhibitor on the pulmonary circulation of Yak living in Tien-Shan Mountains. Background : Rho-kinase inhibitor, fasudil ,effectively decreased pulmonary arterial pressure (PAP) in highlanders having high altitude pulmonary hypertension (HAPH) living in Tien -Shan mountain ( Kojonazarov et al.ERJ 2012; 39(2):496-498). We wonder Rho-kinase actually maintains the pulomonary vascular tone of high-altitude adapted animal, Yak, in Tien-Shan mountains. Methods : Four male domesticated pure breed Yaks (2 years old, BW 200kg) ,and 2 Bull (2 years old, BW200kg) those were born and grown at the altitude 3000m were included in the study. The study was performed at altitude of 3,100m. Mean PAP was measured before and after 30 minutes of intravenous administration of fasudil by Swan-Ganz catheterization. Fasudil (Eril, Asahi Kasei Pharma Corp, Japan) in dose 60 mg in 20ml saline solution were intravenously injected with frequency of 3.3 ml/min. The study was approved by the ethics committee of the NCCIM (Bishkek,Kyrgyzstan) Results : Fasudil, immediately decreased mean PAP in Bull from 88.0±18.0 to 33.0±3.0 mm Hg at post 5min(p=0.01) and maintained decreased level of mean PAP for 30min whereas fasudil had a blunted effect on mean PAP in Yak ; 28.2±4.5mmHg (at start) to 25.1±11.1mmHg( at post 5min) and to 23.2±2.7mmHg (at post 30min). Conclusion : Rho-kinase as a basal vascular tone regulator does not work in pulmonary circulation in Yak. This is one of the reasons why Yak, a high-altitude adapted animal, has a low pulmonary vascular tone despite the hypoxic–air circumstance.

Background At our institution, we generally conduct an ultrathin (UT) (diameter 2.8 mm) bronchoscopy examination followed by a thin (diameter 4.0 mm) bronchoscopy examination using the EBUS-GS method, both with the assistance of virtual bronchoscopic navigation (VBN). Methods From May 1, 2011, to December 31, 2012, we examined 53 cases with an abnormal lung shadow less than 30 mm in diameter with UT bronchoscopy using VBN, followed by thin bronchoscopy with the EBUS-GS method and VBN. Results With assistance from VBN, we diagnosed 33 cases (62.3%) using UT bronchoscopy and 33 cases (62.3%) by thin bronchoscopy with EBUS-GS. Cases with a positive diagnosis were increased to 37 (69.8%) by the use of both. When limited to cancer cases, 32 (72.7%) were found positive using UT bronchoscopy and 32 (72.7%) were positive using thin bronchoscopy with EBUS-GS. The diagnosis rate was elevated to 81.8% (n=36) by use of both methods. Conclusion With the assistance of VBN, the diagnosis rates of UT bronchoscopy and thin bronchoscopy with EBUS-GS were not largely different. However, when both were utilized, the rate increased by 9.1% for cancer and 7.5% for all cases.

Purpose : The aim of this prospective study was to clarify whether dual-time-point [18F]-2-fluoro-2-deoxy- D -glucose positron emission tomography (18F-FDG PET) imaging results are useful to predict long-term survival of idiopathic pulmonary fibrosis (IPF) and fibrotic nonspecific interstitial pneumonia (f-NSIP) patients. Methods : Seventy patients with IPF (n=43) or f-NSIP (n=27) underwent 18F-FDG PET examinations at 2 time points; 60 minutes (early imaging) and 180 minutes (delayed imaging) after 18F-FDG injection. Standardized uptake value (SUV) at each point and the retention index value (RI-SUV) calculated from those were evaluated, then the results were compared with survival and serial trends in pulmonary function indices. Results : The early SUV value for lung lesions in patients with f-NSIP (1.31±0.45) was significantly higher than that in those with IPF (1.09±0.31, P =0.014), whereas the delayed SUV and RI-SUV values were not significantly different. There was no significant difference in survival between the patients groups ( P =0.24). The 3-year survival of all patients (IPF and f-NSIP) negative for RI-SUV (<0%) was 96.7% as compared to 50.8% for those with positive RI-SUV (≥0%; P <0.0001). Positive RI-SUV was shown to be a robust predictor of survival in both groups (IPF, HR 4.67, 95% CI 1.23-17.8, P =0.023; f-NSIP, HR 8.88, 95% CI 1.04-75.9, P =0.046) when compared with baseline FVC, DLCO, and pathological diagnosis. Conclusion : Our results demonstrate that positive RI-SUV is strongly predictive of long-term survival and changes in pulmonary function in patients with IPF or f-NSIP.

The present study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced non-small cell lung cancer who responded well to initial gefitinib, followed by cytotoxic chemotherapy. Twenty subjects were enrolled, and 3 and 6 patients achieved partial response and stable disease, respectively. These findings provide valuable information for the management of previous gefitinib responders.Introduction: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. Materials and Methods: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. Results: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% Cl, 3.21-37.9) and 45% (95% Cl, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% Cl, 0.9-3.1 months) and 12.0 months (95% Cl, 8.0-16.0 months), respectively. Conclusion: These results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders.