Search

We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.

BackgroundSome patients with idiopathic interstitial pneumonia (IIP) show autoimmune features. Interstitial pneumonia with autoimmune features (IPAF) was recently proposed as a research concept in these patients. However, retrospective studies reported conflicting results of its prognosis. Therefore, this study was conducted to prospectively evaluate the clinical significance of autoimmune features in patients with IIP.MethodsThis nationwide multicentre study prospectively enrolled consecutive patients with IIP. At the diagnosis, we systematically evaluated 63 features suggestive of connective tissue diseases using a checklist including symptoms/signs and autoantibodies, which contained most items of the IPAF criteria and followed up with the patients. Clinical phenotypes were included in a cluster analysis.ResultsIn 376 patients with IIP enrolled, 70 patients (18.6%) met the IPAF criteria. The proportion of patients with IPAF was significantly lower in idiopathic pulmonary fibrosis (IPF) than in non-IPF (6.0% vs 24.3%, respectively). During a median observation period of 35 months, patients with IPAF more frequently developed systemic autoimmune diseases and had less frequent acute exacerbation of IIPs than patients with non-IPAF. IPAF diagnosis was significantly associated with better survival and was an independent positive prognostic factor in total and patients with non-IPF. Cluster analysis by similarity of clinical phenotypes identified a cluster in which there was a higher number of women, and patients had more autoimmune features and a better prognosis than other clusters.InterpretationThese observations suggest that some patients with IIP show autoimmune features with distinct characteristics and favourable prognosis. However, we were not able to determine the appropriate therapies for these patients.

Background Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied. Case presentation A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up. Conclusions We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.

Background and objective The efficacy of combination therapy with corticosteroids and CNI, TAC and CsA, for PM/DM-ILD has been described retrospectively. However, it remains unknown which CNI treatment regimens, TAC or CsA regimens, are more effective as initial treatments for patients with PM/DM-ILD. Methods We conducted a prospective multicentre, open-label, randomized, 52-week phase 2 trial. Patients with PM/DM-ILD were randomly allocated to receive PSL plus TAC (TAC group) or PSL plus CsA (CsA group). The primary endpoint was PFS rate in the intention-to-treat population at 52 weeks. The secondary endpoints were OS rate at 52 weeks, changes in pulmonary function tests from baseline to 52 weeks and AE. Results Fifty-eight patients were randomly assigned to the TAC group (n = 30) and the CsA group (n = 28). The PFS rates at 52 weeks were 87% in the TAC group and 71% in the CsA group (P = 0.16). The OS rates at 52 weeks were 97% in the TAC group and 93% in the CsA group (P = 0.50). The %FVC at 52 weeks in the per-protocol populations significantly increased in both groups. None of the patients discontinued the treatment due to AE. Conclusion PSL plus TAC treatment may achieve a better short-term PFS rate compared with PSL plus CsA treatment. Further studies must be conducted to evaluate the long-term efficacy and safety of such treatment.

Eisuke Mochizuki,1 Yoshiihiro Kawai,2 Keisuke Morikawa,1 Yutaro Ito,1 Namio Kagoo,1 Tsutomu Kubota,1 Koshiro Ichijyo,1 Masahiro Uehara,1 Masanori Harada,1 Shun Matsuura,1 Masaru Tsukui,1 Naoki Koshimizu1 1Department of Respiratory Medicine, Fujieda Municipal Hospital, Fujieda 426-8677, Japan; 2Department of Radiology, Fujieda Municipal Hospital, Fujieda 426-8677, JapanCorrespondence: Eisuke Mochizuki Tel +81-54-646-1111Fax +81-54-646-1122Email eisukefukui@gmail.comBackground: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established.Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma.Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44– 89 years) and 11 asthma patients (five males and six females; median age 55; range: 32– 75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests.Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score < 8).Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.Keywords: COPD, asthma four-dimensional dynamic-ventilation CT

Background Nivolumab, a programmed death 1 (PD-1) immune checkpoint inhibitor, has been shown to improve survival in non-small cell lung cancer (NSCLC). The possible involvement of PD-1 axis in the pathogenesis of inflammatory lung disease, such as chronic obstructive pulmonary disease (COPD) has also been reported. However, effects of PD-1 blockade on the respiratory system remain unknown. Objectives This prospective study aimed to investigate whether inhibition of the PD-1 axis altered lung inflammation and pulmonary function in NSCLC patients with and without COPD. Method This was a prospective multi-center study. Measurements of fractioned exhaled nitric oxide (FeNO) and pulmonary function were performed before and after 4 cycles of nivolumab therapy. Results A total of 137 patients with NSCLC were initially enrolled, and subsequently 95 patients (41 COPD and 54 non-COPD) receiving 4 cycles of nivolumab administration were included. After anti-PD-1 therapy, FeNO levels were significantly elevated together with increase in peripheral eosinophils. Interestingly, significant FeNO elevation was only found in COPD patients without increased peripheral eosinophils, but this was not the case in non-COPD patients. Additionally, COPD patients exhibited significant increases in FVC and FEV1 but no changes in dyspnea scales, and acute exacerbation did not occur during the therapy. Conclusion Our observations suggest that anti-PD-1 therapy changed FeNO levels and pulmonary function in NSCLC patients. This therapy does not worsen COPD in terms of symptoms, pulmonary function, or acute exacerbation.

Background Allergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS) are characterized by hyper-responsiveness of the respiratory tract and the nasal cavity and paranasal sinuses, respectively to Aspergillus species and AFRS causes chronic rhinosinusitis. Herein, we report the first case of sinobronchial allergic mycosis (SAM) syndrome, defined as ABPA with concomitant AFRS, caused by Aspergillus fumigatus patient > 80 years. Case presentation An 82-year-old male with interstitial pneumonia who returned for follow-up exhibited high-attenuation mucus plug in the right intermediate bronchial trunk, infiltration in the right lung field, and right pleural effusion on regular chest computed tomography (CT). We found unilateral central bronchiectasis in the right upper lobe. Similarly, CT scan of the paranasal sinuses revealed high-attenuation mucus plugs in left ethmoid sinuses. Biopsy specimens from the plugs in the right intermediate bronchial trunk and the left ethmoid sinuses revealed allergic mucin with layers of mucus eosinophils, eosinophil-predominant mixed inflammatory cell infiltrate and Aspergillus hyphae. The patient fulfilled all the major criteria for ABPA and AFRS, and was diagnosed with SAM syndrome. CT scan of the lung and paranasal sinuses revealed apparent amelioration after oral steroid therapy. Conclusion Despite mostly reported in relatively young patients, SAM syndrome can occur in elderly individuals as well.

Rationale: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. Patient Concerns and Diagnoses: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. Intervention and Outcome: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. Lessons: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.

Epidermal growth factor receptor (EGFR) exon 20 insertion is not associated with sensitivity to EGFR tyrosine kinase inhibitors and chemotherapy. Here, we report the case of a 41-year-old man who presented a right lower lobe nodule and mediastinal lymph node enlargement diagnosed as EGFR exon 20 insertion adenocarcinoma with high-expression programmed cell death ligand 1 (PD-L1). He showed stable disease to chemoradiation treatment at the primary tumor site. However, durvalumab treatment has good response. Non-small cell lung cancer with EGFR exon 20 insertion and high PD-L1 expression may be treated with immunotherapy exposure.

Background: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare form of idiopathic interstitial pneumonia that is characterized by predominantly upper lobe pleural and subpleural lung parenchymal fibrosis. Pneumothorax is one of the major respiratory complications in PPFE patients; however, its clinical features are poorly understood. Objective: We aimed to investigate the complication of pneumothorax in patients with idiopathic PPFE. Methods: A retrospective multicenter study involving 89 patients who had been diagnosed with idiopathic PPFE was conducted. We investigated the cumulative incidence, clinical features, and risk factors of pneumothorax after the diagnosis of idiopathic PPFE. Results: Pneumothorax developed in 53 patients (59.6%) with 120 events during the observation period (41.8 ± 35.0 months). The cumulative incidence of pneumothorax was 24.8, 44.9, and 53.9% at 1, 2, and 3 years, respectively. Most events of pneumothorax were asymptomatic (n = 85; 70.8%) and small in size (n = 92; 76.7%); 30 patients (56.6%) had recurrent pneumothorax. Chest drainage was required in 23 pneumothorax events (19.2%), and a persistent air leak was observed in 13 (56.5%). Patients with pneumothorax were predominantly male and frequently had pathological diagnoses of PPFE and prior history of pneumothorax and corticosteroid use; they also had significantly poorer survival than those without pneumothorax (log-rank test; p = 0.001). Multivariate analysis revealed that a higher residual volume/total lung capacity ratio was significantly associated with the development of pneumothorax after the diagnosis. Conclusion: Pneumothorax is often asymptomatic and recurrent in patients with idiopathic PPFE, leading to poor outcomes in some cases.

A 63-year-old woman presented with a fever, eruption, and sterile pyuria. A cystoscopic examination revealed submucosal nodular lesions in the trigone of the bladder, and a biopsy specimen showed epithelioid cell granulomas in the lamina propria of the bladder. Mycobacterium avium grew in the urine culture. Other organ involvement, such as the lungs, spleen, bones, muscles, and pelvic lymph nodes, was observed on radiological examinations, and M. avium was isolated from some organ lesions. Interferon-γ-neutralizing autoantibodies were detected in the patient's serum. Therefore, the patient was diagnosed with disseminated M. avium infection, which was resolved with antimycobacterial treatment.

Immunoglobulin type G4 -related disease (IgG4-RD) is known as a chronic systemic inflammatory disease, which is sometimes associated with lung cancer. However, the detailed association between IgG4-RD and lung cancer in clinical settings is still poorly understood. An 80-year-old man was diagnosed with progressive lung adenocarcinoma carrying an EGFR point mutation at L858R, and osimertinib treatment was administered. Two months later, although osimertinib treatment showed good response to the primary tumor, fever and anorexia appeared, and multiple lymph nodes, in particular in the left axillary, became swollen. Ultrasonography-guided biopsy of the axillary lymph node revealed infiltration of lymphocytes with IgG4-positive plasma cells and fibrosis. Serum IgG4 levels were also increased. These results suggested that the multiple swollen lymph nodes were not metastasis, but IgG4-related disease. Based on these results, therapy using prednisolone was initiated. Multiple lymphadenopathy gradually decreased, and his symptoms improved. Currently, his good responses to osimertinib treatment have been maintained. Like in our case, multiple lymphadenopathy with IgG4-positive plasma cell infiltration during successful anti-cancer treatment is quite rare. In this case, it was hypothesized that anti-cancer treatment with osimertinib induced IgG4-positive plasma cell infiltration in multiple lymph nodes. When lymphadenopathy occurs during lung cancer treatment, IgG4-RD has to be considered other than lung cancer metastasis.

Background: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a distinctive interstitial pneumonia with upper lobe predominance that shows unique morphological features, and a relatively poor prognosis. However, patinets have various clinical presentations with a heterogeneous clinical course. Cluster analysis modeling is a valuable tool in identifying distinct clinical phenotypes in heterogeneous conditions. Methods: Using cluster analysis, novel PPFE phenotypes were identified among subjects from multicenter cohort, and outcomes were stratified according to phenotypic clusters. Results: Among subjects with complete data for baseline variables (N = 84), four clusters were identified. Cluster 1 (younger male subjects with coexistent non-UIP pattern) had the highest baseline FVC and diffusion capacity of the lung for carbon monoxide (DLCO). Cluster 2 (elderly female subjects non-smokers with lowest BMI) had intermediate FVC and DLCO. Cluster 3 (elderly male smokers with coexistent UIP pattern) had the lowest baseline FVC. Cluster 4 (younger male smokers without lower lobe lesion) had relatively higher baseline FVC and DLCO. In survival outcome, patients in Cluster 3 had significantly poor prognosis than Cluster 1, 2, and 4 (p Conclusions: Among diverse progressive idiopathic PPFE patients, cluster analysis using baseline characteristics identified four distinct clinical phenotypes that might predict survival outcome.

Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a distinctive interstitial pneumonia with upper lobe predominance that shows unique morphological features among idiopathic interstitial pneumonias (IIPs). Affected patients have a variety of clinical presentations with heterogeneous clinical courses. Cluster analysis is a valuable tool for identifying distinct clinical phenotypes under heterogeneous conditions. This study aimed to identify the phenotypes of patients with idiopathic PPFE. Using cluster analysis, novel PPFE phenotypes were identified among subjects from our multicenter cohort, and outcomes were stratified according to phenotypic clusters. Among the subjects with baseline data (N = 84), four clusters were identified. Cluster 1 included younger male subjects with coexisting non-UIP-like patterns. Cluster 2 included elderly female nonsmokers with low body mass index (BMI). Cluster 3 included elderly male smokers with a coexisting IP-like pattern. Cluster 4 included younger male smokers without lower lobe lesions. Patients in cluster 3 had significantly worse survival outcomes than those in clusters 1, 2, and 4 (p &lt, 0.001, p = 0.0041, and p = 0.0155, respectively). Among idiopathic PPFE patients, cluster analysis using baseline characteristics identified four distinct clinical phenotypes that might predict survival outcomes.

Sarcoidosis affects multiple organs and rarely has unusual manifestations. A 78-year-old woman was referred to our hospital for coughing symptoms. A chest computed tomography (CT) scan revealed bilateral diffuse miliary patterns and right pleural effusion. Bronchoscopy showed multiple nodules in the carina and the bronchus intermedius. A CT scan of her abdomen revealed hypovascular lesions involving the pancreatic head and body. A transbronchial lung biopsy, bronchial mucosal biopsy, and endoscopic ultrasound-guided fine-needle aspiration of the pancreatic mass demonstrated non-caseating granulomas. We diagnosed the patient with sarcoidosis. She received no treatment for sarcoidosis and has been followed up for one year, during which no pulmonary disease progression had been observed and the pancreatic masses partially regressed.

Objectives Single agent maintenance therapy is widely accepted for advanced non-squamous non small cell lung cancer (NSCLC). However, there is no consensus on the initial and maintenance phase regimens, and the clinical benefit of adding bevacizumab to cytotoxic drugs in the maintenance phase remains unclear. Methods Chemotherapy-naive patients with non-squamous NSCLC were randomly assigned to maintenance therapy with pemetrexed and bevacizumab or pemetrexed alone, after achieving disease control after four cycles of induction therapy with carboplatin (area under the curve = 6), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg). The primary end-point was 1-year progression-free survival (PFS) rate. Results One hundred ten patients were enrolled in the study, with 55 patients assigned to the two groups. The mean 1-year PFS rate was 43.9% (95% confidence interval [CI]: 29.6–59.2%) in the combination maintenance group and 35.2% (95% CI: 22.1–51.0%) in the pemetrexed maintenance group, and the difference was not significant (p = 0.433). Median PFS measured from enrolment was 11.5 months (95% CI: 7.1–19.0) in the combination maintenance group and 7.3 months (95% CI: 5.7–14.1, hazard ratio: 0.73, 95% CI: 0.44–1.19, log-rank p = 0.198) in the pemetrexed maintenance group. Nasal haemorrhage, hypertension, and proteinuria were significantly more frequent in the combination maintenance group, but they were mild and tolerable. Conclusion Both maintenance therapy with pemetrexed alone and pemetrexed and bevacizumab in combination were feasible in patients with non-squamous NSCLC who have achieved disease control after induction therapy with carboplatin, pemetrexed, and bevacizumab. According to the selection design, differences in the superiority between these maintenance therapies were not demonstrated.

Inhaled corticosteroids are widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, their use has been questioned for appropriate dose and a possible increased risk of pneumonia. Here, we reviewed patients with COPD who had received fluticasone–salmeterol combination treatment using data from a linked electronic medical record database. A total of 180 patients received salmeterol with 250 µg fluticasone propionate twice daily and 78 received salmeterol and 100 µg fluticasone propionate twice daily. In both groups, there was no difference in the improved forced expiratory volume in 1 second and COPD assessment test score and the proportion of patients with exacerbations. Although the incidence of common toxicity was approximately equal, that of pneumonia was much higher in the 250 µg group (8.9% vs 1.3%, P=.01). The beneficial effects of inhaled corticosteroids might be obtained at lower doses.

Background There are few reports about the factor influencing the prognosis of high-grade neuroendocrine carcinoma. In this study, we evaluated surgical outcome of clinical stage I high-grade neuroendocrine carcinoma. Methods Patients who underwent curative surgery for high-grade neuroendocrine tumors of the lung in clinical stage I were included in this study. We retrospectively analyzed 27 consecutive patients. The aim of this study was to clarify the clinical course of the disease after surgery and what factors influence the prognosis. Results Twenty-two patients have small cell carcinoma, and 5 patients have large cell neuroendocrine carcinoma. Patients who could undergo surgery within 60 days after the first visit (p

Background Although the accurate diagnosis of pleuroparenchymal fibroelastosis (PPFE) requires pathologic evaluation, this diagnosis is often suggested when the radiologic findings are consistent with typical PPFE and when pulmonary apical cap, which radiologically and pathologically mimics PPFE, can be excluded by confirming disease progression. The aim of this study was to evaluate the validity of the clinical diagnosis of idiopathic PPFE. Methods We recruited 44 patients with idiopathic PPFE according to our modified diagnostic criteria: 1) a radiologic PPFE pattern (i.e., bilateral subpleural dense consolidation with or without pleural thickening in the upper lobes and less marked or absent involvement of the lower lobes), 2) radiologic confirmation of disease progression, and 3) exclusion of other lung diseases with identifiable etiologies. The patients' baseline characteristics and clinical course were reviewed. Results The median age was 70 years, and 28 patients were males. The majority revealed emaciation, hypercapnia, and a high ratio of residual volume to total lung capacity. On chest computed tomography, 39 patients showed abnormal shadows in the lower lobes; more than half were classified as having usual interstitial pneumonia (UIP)/possible UIP pattern. Pneumothorax was the most frequent complication (33/44). The median overall survival time after diagnosis was 35.3 months. The presence of lower lobe UIP/possible UIP pattern did not show a significant prognostic impact. Conclusions Using our diagnostic criteria, we could recruit relatively many patients with similar characteristics to those of idiopathic PPFE patients in the literature. The possibility of clinical diagnosis of idiopathic PPFE should be further discussed.

Chronic eosinophilic pneumonia (CEP) is characterized by the accumulation of eosinophils in the lung with unknown etiology. Although systemic corticosteroid administration leads to dramatic improvement, nearly half the patients with CEP experience relapse and some develop persistent impairment of pulmonary function. However, predictive factors for this persistent impairment have not been determined.To investigate the occurrence of persistent impairment of pulmonary function in CEP and determine its predictive factors.This observational study consisted of 133 consecutive patients with CEP who were followed for longer than 1 year. Spirometry was performed at the time of diagnosis and at follow-up.During the observational period (6.1 ± 4.1 years), relapse occurred in 75 patients (56.4%). Remarkably, 42 patients (31.6%) had a persistent pulmonary function defect (27 obstructive, 10 restrictive, and 4 obstructive and restrictive cases) at the last evaluation. Logistic analyses showed that the relapse was associated with neither persistent obstructive nor restrictive defects. Persistent obstructive defect was significantly associated with the comorbidity of asthma and obstructive defect at the initial CEP diagnosis, whereas persistent restrictive defect was significantly related to reticulation at high-resolution computer tomography and restrictive defect at diagnosis.Persistent impairment of pulmonary function is common in CEP. Concurrent asthma and obstructive defects at diagnosis were predictors for persistent obstructive impairments, whereas reticulation at high-resolution computer tomography and restrictive defect at diagnosis predicted persistent restrictive impairment. Attention should be paid to these persistent impairments in the management of CEP.http://www.umin.ac.jp/ctr/index-j.htm Identifier: UMIN000019092 (principal investigator, Takafumi Suda, MD, PhD).

Objective Interstitial lung disease (ILD) is a condition characterized by a higher mortality rate in primary Sjogren's syndrome (pSS). However, factors influencing the outcome of patients with pSS-associated ILD remain unclear. The aim of the present study was to evaluate predictive factors associated with a worse prognosis in pSS-ILD. Methods This retrospective study included 99 consecutive patients with pSS-ILD. Clinical characteristics, laboratory findings, and pulmonary function tests at the time of diagnosis were analyzed. Chest HRCT images were reviewed by two experienced chest radiologists. Prognostic factors were assessed by univariate and multivariate analyses, using Cox proportional hazards regression model. Results Median age was 68 years (73% women). In the total patient population, the 5- and 10-year survival rates were 89.8% and 79.0%, respectively. Univariate analysis revealed a significant association between prognosis and age, serum Krebs von den Lungen-6 (KL-6) levels, and %FVC. None of the chest HRCT findings were related to patient outcomes. Based on multivariate analyses adjusted by age and gender, lower levels of %FVC and higher levels of KL-6 were significantly associated with poor outcomes. Using optimal cutoff levels, according to receiver operating characteristic curve analyses, KL-6 > 800 U/mL were significantly associated with worse prognosis (HR: 2.91, 95% CI: 1.04–8.10). Patients with elevated serum KL-6 levels (>800 U/mL) showed a higher mortality rate than those without elevated serum KL-6 levels (p = 0.02). Conclusions Lower %FVC and higher serum KL-6 levels are predictive factors for poor outcome in patients with pSS-ILD.

RATIONALE: Since high-grade neuroendocrine tumors are rapidly progressive, most cases are inoperable when diagnosed. There are few reports about the prognosis of patients or the course of the disease after surgery. OBJECTIVES: To clarify the clinical course of the disease after surgery and factors influencing the prognosis. METHODS: We retrospectively assessed 27 patients receiving surgery for small cell carcinoma (22 cases) and large neuroendocrine carcinoma (5 cases) from January 2005 through January 2015 at our hospital. RESULTS: Patients were all male, with an average age of 70.9 years. Of the 27 patients, 22 had received postoperative adjuvant chemotherapy. Median progression-free survival (PFS) and overall survival (OS) were 1.1 and 5.5 years, respectively. Ten patients were recurrence-free. Ten patients who underwent surgery within 60 days after the diagnosis demonstrated a better prognosis regarding OS (p CONCLUSIONS: Early surgical resection for high-grade neuroendocrine carcinoma stage I may lead to a better prgonosis.

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naive patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

A 73-year-old man with underlying chronic renal failure, angina pectoris, chronic heart failure, and respiratory failure reporting three-day appetite loss, fever, and drowsiness was admitted for lower right lung pneumonia. Despite antibiotic administration, infiltration progressed to the entire right lung and upper left lung after 12 hours, and he developed acute respiratory distress syndrome (ARDS) and multiple organ failure. Respirator ventilation and continuous hemodiafiltration (CHDF) failed to halt this progression and he died on hospital day 3. Acinetobacter baumannii was cultured from bronchoalveolar lavage fluid and the postmortem lung specimen, indicating that his severe community-acquired pneumonia was due to A. baumannii. Microscopically, the lung specimen showed prominent cellular alveolar exudate and partial hyaline membrane with suppurative pneumonia. Although A. baumannii is considered the causative agent in nosocomical pneumonia, community-acquired pneumonia due to A. baumannii is very rare. This is, to our knowledge, the first report in Japan. In the subtropical zone, A. baumannii is recognized as an important cause of severe community-acquired pneumonia. Given the apparent progress of global warming, physicians in Japan would do well to familiarize themselves with subtropical disease causes such A. baumannii when managing severe community-acquired pneumonia.

Objectives Although antiemetic management has improved, better control of chemotherapy-induced nausea and vomiting (CINV), particularly during the delayed phase, is needed. The benefit of combination therapy using dexamethasone and the second-generation 5-hydroxytryptamine-3 receptor antagonist palonosetron compared with that of other such receptor antagonists in carboplatin-based chemotherapy is unclear. The effectiveness of adding aprepitant for CINV treatment in moderate emetogenic chemotherapy is also unknown. We compared the efficacy and safety of triple antiemetic therapy using aprepitant, palonosetron, and dexamethasone with that of double antiemetic therapy using palonosetron and dexamethasone in patients with advanced non-small-cell lung cancer receiving carboplatin-containing chemotherapy. Methods Chemotherapy-naive patients with non-small-cell lung cancer were enrolled in this prospective controlled study. Eighty patients were randomly assigned to groups receiving either double antiemetic therapy with palonosetron and dexamethasone, or triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone. Complete response rate (no vomiting episode and no rescue therapy) was evaluated as the primary endpoint during the 5-day post-chemotherapy period. Results The aprepitant add-on and double therapy groups showed overall complete response rates of 80.5% (95% confidence interval [CI]: 68.4–92.6%) and 76.9% (95% CI: 63.7–90.1%; odds ratio [OR]: 0.81; 95% CI; 0.27–2.36; p = 0.788), respectively. Complete responses in the acute and delayed phases and overall incidences of treatment-related adverse events were similar between groups. Conclusion According to the selection design, triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone was not considered as an option for further studies.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are key drugs in the treatment of non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. We assessed the efficacy and safety of one EGFR tyrosine kinase inhibitor, erlotinib, in elderly Japanese patients with EGFR-mutated NSCLC.Elderly patients aged 75 or older with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) were enrolled in this prospective phase II trial. Patients received 150 mg erlotinib per day orally. The primary end point was the overall response rate.Between March 2013 and November 2014, 32 patients were enrolled with median age 80 years. All tumors had adenocarcinoma histology, and 20 patients (62.5 %) had an L858R mutation. The response rate was 56.3 % [95 % confidence interval (CI) 39.4-72.0 %], and the disease control rate was 90.6 % (95 % CI 75.2-97.6 %). Median progression-free survival was 15.5 months (95 % CI 11.2-not reached). Skin disorder was the most common adverse event, and grade 4 drug-related interstitial lung disease occurred in one patient.Erlotinib is effective and tolerated in elderly patients with EGFR mutation-positive NSCLC.

Here, we report the case of a patient with small-cell lung carcinoma (SCLC) who developed the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This syndrome may be associated with chemotherapy-induced tumour lysis. Our patient was successfully treated with tolvaptan. A 70-year-old man was diagnosed with SCLC and was treated with carboplatin and etoposide. Episodes of hyponatremia occurred after every four cycles of chemotherapy that achieved tumour reduction; however, the hyponatremia was improved by temporary administration of tolvaptan. In SIADH associated with chemotherapy-induced tumour lysis, tolvaptan may improve hyponatremia and enable the continued administration of effective chemotherapy.

Background Chronic eosinophilic pneumonia (CEP) is characterized by the accumulation of eosinophils in the lung with unknown etiology. Although systemic corticosteroid administration leads to dramatic improvement, nearly half the patients with CEP experience relapse and some develop persistent impairment of pulmonary function. However, predictive factors for this persistent impairment have not been determined. Objective To investigate the occurrence of persistent impairment of pulmonary function in CEP and determine its predictive factors. Methods This observational study consisted of 133 consecutive patients with CEP who were followed for longer than 1 year. Spirometry was performed at the time of diagnosis and at follow-up. Results During the observational period (6.1 ± 4.1 years), relapse occurred in 75 patients (56.4%). Remarkably, 42 patients (31.6%) had a persistent pulmonary function defect (27 obstructive, 10 restrictive, and 4 obstructive and restrictive cases) at the last evaluation. Logistic analyses showed that the relapse was associated with neither persistent obstructive nor restrictive defects. Persistent obstructive defect was significantly associated with the comorbidity of asthma and obstructive defect at the initial CEP diagnosis, whereas persistent restrictive defect was significantly related to reticulation at high-resolution computer tomography and restrictive defect at diagnosis. Conclusion Persistent impairment of pulmonary function is common in CEP. Concurrent asthma and obstructive defects at diagnosis were predictors for persistent obstructive impairments, whereas reticulation at high-resolution computer tomography and restrictive defect at diagnosis predicted persistent restrictive impairment. Attention should be paid to these persistent impairments in the management of CEP. Trial Registration http://www.umin.ac.jp/ctr/index-j.htm Identifier: UMIN000019092 (principal investigator, Takafumi Suda, MD, PhD).

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD. METHODS: The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively. RESULTS: The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p

e20554Background: Maintenance therapy has been widely accepted as a standard therapy in non-squamous non-small-cell lung cancer (NSCLC). However, the clinical benefit of maintenance therapy for squ...

e20504Background: Maintenance therapy with pemetrexed is accepted as a standard therapy for advanced non-squamous non-small-cell lung cancer (NSCLC). Bevacizumab improves the efficacy of chemothera...

e20566Background: The number of elderly patients with non-small-cell lung cancer (NSCLC) is increasing in advanced countries. EGFR mutation is common in elderly patients as well as in younger patie...

e20557Background: Chemotherapy-induced nausea and vomiting (CINV) remains a challenging issue in cancer treatment. Carboplatin is widely used in multi-organ cancers; however, clinical benefit of ap...

gamma-Irradiation of gelatin and collagen hydrogels can be used for sterilization and mechanical stabilization, providing biomaterials suitable for both tissue engineering and drug-delivery systems. Controversial results have been reported regarding the extent of irradiation-induced cross-linking and degradation, which depend on both protein concentration and irradiation dose. In this work the relative contributions of these processes were studied for irradiation doses between 0 and 1.0 kGy and concentrations between 0.3% and 5% using size-exclusion chromatography (SEC) with multi-angle laser light scattering (MALLS) and viscosity detection, as well as SDS-PAGE. It was demonstrated that chain degradation and cross-linking occur simultaneously in fish gelatin (FG), porcine gelatin (PG) and porcine collagen (PC), by the gradual appearance of protein fragments (10-80) x 10(3) concomitant with the formation of structures of high molecular weight. FG and PG behaved rather similarly, despite the fact they were irradiated and analyzed above and below their denaturation temperatures, respectively, suggesting little or no influence of molecular ordering under the conditions used. PC showed an increasing amount of degradation products following heat treatment prior to SEC-MALLS, suggesting that chain cleavage may occur within ordered collagen structures without complete release of the protein fragments.