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Background Predicting the incidence of chemotherapy‐triggered acute exacerbation of interstitial lung disease (AE‐ILD) in patients with lung cancer is important because AE‐ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation‐based index composed of serum levels of C‐reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE‐ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. Methods Medical records of patients who received platinum‐based first‐line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE‐ILD and overall survival (OS) between GPS 0, 1, and 2. Results Among our cohort of 31 patients, six (19.3%) experienced chemotherapy‐triggered AE‐ILD. The AE‐ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE‐ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p, The Glasgow prognostic score (GPS) tends to be associated with incidence of acute exacerbation of interstitial lung disease (AE‐ILD) (p = 0.082). GPS 2 is an independent risk factor for chemotherapy‐triggered AE‐ILD and prognosis in SCLC patients. GPS may be used as a guide to distinguish chemotherapy‐tolerant patients from those at high risk of AE‐ILD.

Synovial sarcoma is a high-grade soft tissue sarcoma that occurs primarily in the deep soft tissue of extremities, and primary colorectal synovial sarcoma is extremely rare. In this report, we present a synovial sarcoma mostly located within the mucosa of the sigmoid colon. The patient was a man in his forties with a germline deletion in the MSH2 gene. He had experienced undifferentiated pleomorphic sarcoma of the left forearm 7 years before and adenocarcinoma of the transverse colon 6 years before, both of which were successfully treated and exhibited no recurrence to date. A surveillance colonoscopy for Lynch syndrome revealed the tumor which had a submucosal tumor-like appearance with central erosion and endoscopic resection was performed. Histologically, it was composed of monotonous proliferation of spindle cells arranged in cellular fascicles; these findings were compatible with monophasic fibrous synovial sarcoma. In the tumor cells, the presence of the SS18-SSX1 fusion gene was confirmed. Protein expression of mismatch repair genes was intact in the tumor cells, indicating the association between microsatellite instability and synovial sarcoma was weak. The present case highlights a rare primary site of synovial sarcoma in a patient with Lynch syndrome.

Background: While recent evidence has suggested that sarcopenia could predict chemotoxicity, its association with chemotherapy-triggered interstitial lung disease (ILD) exacerbations has yet to be investigated. Thus, the present study sought to determine whether sarcopenia could predict ILD exacerbations and overall survival (OS) in patients with ILD-complicated non-small cell lung cancer (NSCLC).Methods: From January 2010 to July 2020, 74 patients with ILD-complicated NSCLC who received chemotherapy were retrospectively investigated. After categorizing patients according to the presence or absence of sarcopenia based on the psoas muscle index, ILD exacerbation rates and OS were evaluated.Results: Among the included patients, 39 were included in the sarcopenia group. Moreover, 17 (22.9%) patients developed ILD exacerbations, with the sarcopenia and no-sarcopenia groups having an exacerbation rate of 33.3% and 11.4%, respectively (p = 0.025). Multivariate analysis identified sarcopenia as an independent predictor of ILD exacerbations (p = 0.039). Furthermore, patients with sarcopenia demonstrated a significantly shorter median OS compared to those without the same (9.2 vs. 13.3 months; p = 0.029).Conclusions: Sarcopenia predicted chemotherapy-triggered ILD exacerbation and OS in patients with ILD-complicated NSCLC, suggesting its utility in determining treatment approaches.Classifications: Pneumonology

Highlights • Favipiravir is undergoing clinical trials for treating COVID-19. • Drug fever is difficult to diagnose in patients with febrile illnesses. • We report 2 cases of favipiravir-induced drug fever in patients with COVID-19., Favipiravir, an antiviral agent, is undergoing clinical trials for treating novel coronavirus disease 2019 (COVID-19). We report two cases of COVID-19 with favipiravir-induced fever. In both cases, pyrexia was observed following administration of favipiravir despite symptoms of COVID-19 improving. No other cause for the fever was evident after careful physical examination and laboratory investigation. Once favipiravir was discontinued, the fever subsided in both patients. To our knowledge, this is the first report of favipiravir-induced fever.

A 69‐year‐old man with a history of type 2 diabetes and high blood pressure was diagnosed with coronavirus disease 2019 (COVID‐19). He had hyperferritinaemia and respiratory failure. Despite the initiation of favipiravir and high‐dose corticosteroid and ceftriaxone, his respiratory failure progressed and serum ferritin levels increased. After polymyxin B‐immobilized fibre column direct haemoperfusion (PMX‐DHP) therapy, there was improvement of the respiratory failure and hyperferritinaemia. We report the first case of COVID‐19‐induced hyperferritinaemia and severe respiratory failure successfully treated by PMX‐DHP., We report the first case of coronavirus disease 2019 (COVID‐19)‐induced hyperferritinaemia and severe respiratory failure successfully treated by polymyxin B‐immobilized fibre column direct haemoperfusion (PMX‐DHP) therapy.

To identify prognostic factors for axial length (AL) elongation and incidence of posterior staphyloma (PS) in adult Japanese patients with high myopia.Retrospective, observational cohort study.Six-year follow-up data for 345 patients (620 eyes with AL ≥ 26.5 mm and spherical equivalent [SE] ≤- 8.00 diopters) admitted to the Tokyo Medical and Dental University Hospital from 2007 to 2017 were analyzed retrospectively. Main outcome measures were change in AL from baseline, factors associated with AL, categorization of eyes with high myopia, factors associated with incidence of PS, and impact of PS on myopic maculopathy and visual function.The mean annual increase in AL was 0.03 mm. Presence of optic nerve disc conus (P = .025), steeper corneal curvature, lower SE, and decreased choroidal thickness (CT) (all P.001) were associated with increased AL in univariate and multivariate analyses. Younger age (P = .003) and no use of intraocular pressure-lowering medications (P = .046) were associated with increased AL. Eyes with high myopia were categorized using factor analysis as associated with glaucoma, severe pathologic myopia, and mild-to-moderate pathologic myopia. Older age, increased AL, glaucoma, and choroidal thinning (all P ≤ .001) were identified as significant risk factors for the incidence of PS in univariate and/or multivariate analyses. Incidence of PS was a precursor for myopic maculopathy and visual field defects.Optic nerve disc conus, steeper corneal curvature, lower SE, decreased CT, and no use of intraocular pressure-lowering medications were prognostic factors for increased AL. Older age, increased AL, glaucoma, and decreased CT were prognostic factors for PS.

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=-0.3373, P=0.0078 and r=-0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Background: Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma.Methods: Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Results: Serum NGAL levels in patients with asthma and obstructive ventilatory disorder were higher than those in patients with asthma without obstructive ventilatory disorder (76.4 ± 51.4 ng/mL vs 39.3 ± 27.4 ng/mL, p=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 25% of vital capacity %predicted (r=-0.3373, p=0.0089 and r=-0.2900, p=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory disorder.Conclusion: Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory disorder. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype characterized by both biological and clinical heterogeneity. In refractory cases, complete response/complete response unconfirmed rates in salvage therapy remain low. We performed whole-exome sequencing of DLBCL in a discovery cohort comprising 26 good and nine poor prognosis cases. After candidate genes were identified, prognoses were examined in 85 individuals in the DLBCL validation cohort. In the discovery cohort, five patients in the poor prognosis group harbored both a TP53 mutation and 17p deletion. Sixteen mutations were identified in OSBPL10 in nine patients in the good prognosis group, but none in the poor prognosis group. In the validation cohort, TP53 mutations and TP53 deletions were confirmed to be poor prognostic factors for overall survival (OS) (P = 0.016) and progression-free survival (PFS) (P = 0.023) only when both aberrations co-existed. OSBPL10 mutations were validated as prognostic markers for excellent OS (P = 0.037) and PFS (P = 0.041). Significant differences in OS and PFS were observed when patients were stratified into three groups—OSBPL10 mutation (best prognosis), the coexistence of both TP53 mutation and TP53 deletion (poorest prognosis), and others. In this study, the presence of both TP53 mutation and 17p/TP53 deletion, but not the individual variants, was associated with poor prognosis in DLBCL patients after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or similar regimens. We also identified OSBPL10 mutation as a marker for patients with excellent prognosis in the R-CHOP era.

A 35-year-old Japanese man who had experienced hoarseness for 10 years presented with a vocal cord lesion. A gross examination revealed a left vocal cord polyp occupying two-thirds of the vocal space. The endoscopically resected lesion contained scattered atypical fibroblastic, stellate, or ganglion-like cells with mucoid stroma. Vacuolated cells were also seen. Lymphoplasmacytic infiltrate was largely undetectable. A vocal cord polyp was first suspected, but well-differentiated liposarcoma and inflammatory myofibroblastic tumor (IMT) were included in the differential diagnoses. The tumor cells were positive for anaplastic lymphoma kinase (ALK), calponin, and vimentin, and negative for other smooth muscle markers by immunohistochemistry. Structures resembling myofibroblasts were not observed by electron microscopy, which confirmed abundant rough endoplasmic reticulum in the tumor cells and accumulated lipid droplets in some tumor cells. ALK gene rearrangement was detected by fluorescence in situ hybridization, and TIMP3-ALK fusion was confirmed by 5' rapid amplification of cDNA ends. We diagnosed the lesion as an IMT, and an ALK-rearranged stellate cell tumor may be postulated. This is the first report of a fusion partner gene of ALK in a case of laryngeal IMT.

Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.

Background Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) has to be reported to often cause rapidly progressive interstitial lung disease (RP-ILD) especially in East Asian countries. Even with the recommended rapid administration of immunosuppressive agents with high-dose corticosteroids, intravenous pulse cyclophosphamide, and calcineurin inhibitors, the prognosis of anti-MDA5 Ab–related RP-ILD is poor. Plasma exchange (PE) has been reported to be effective for steroid-refractory RP-ILD with anti-MDA5 Ab. However, the timing, frequency, and interval of PE for the treatment of RP-ILD with anti-MDA5 Ab have not yet been established. Case presentation We report two cases of RP-ILD with anti-MDA5 Ab treated by early intervention of PE combined with immunosuppressive treatment. Blood biomarkers including titers of anti-MDA5 Ab, serum KL-6 and ferritin were promptly decreased after each session of PE. Clinical symptoms, oxygenation and chest computed tomography abnormalities were completely improved after immunosuppressive treatment with PE. Conclusion Early intervention of PE combined with immunosuppressive treatment may prevent the development to lethal severe respiratory failure in RP-ILD with anti-MDA5 Ab.

There are concerns regarding overtreatment in papillary thyroid carcinoma (PTC). BRAF V600E and TERT promoter mutations play important roles in the development of PTC. However, initial surgical approaches for PTC based on genetic characteristics remain unclear. The present study aimed to identify genetic mutations as predictors of prognosis and to establish proper indications for lobectomy (LT) in patients with 1&ndash, 4 cm intrathyroidal PTC. Prospectively accumulated data from 685 consecutive patients with PTC who underwent primary thyroid surgery at the Cancer Institute Hospital, Tokyo, Japan, between 2001 and 2012 were retrospectively reviewed. Of the 685 patients examined, 538 (78.5%) had BRAF V600E mutation and 133 (19.4%) had TERT promoter mutations. Patients with TERT promoter mutations displayed significantly worse outcomes than those without mutations (10-year cause-specific survival (CSS): 73.7% vs 98.1%, p &lt, 0.001, 10-year disease-free survival (DFS): 53.7% vs 93.3%, p &lt, 0.001). As for extent of thyroidectomy among TERT mutation-negative patients with 1&ndash, 4 cm intrathyroidal PTC, patients who underwent LT showed no significant differences in 10-year CSS and 10-year DFS compared to patients who had total thyroidectomy (TT) under propensity score-matching. Avoiding TT for those patients indicates a possible pathway to prevent overtreatment and reduce postoperative complications.

We prospectively showed that when anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) is sensitive enough and appropriately interpreted, it can be a stand-alone diagnostic for ALK inhibitor therapies. Our data will further spread and promote IHC for the screening of patients who will benefit from ALK inhibitor therapy, and cut the time and money costs for that purpose., Background Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. Patients and methods In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. Result ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. Conclusions Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. Registration number JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center).

A 36-year-old male was found two nodules in the right lower lobe of the lung. After the surgical resection, both lesions were diagnosed as invasive adenocarcinomas. One lesion was primarily lepidic growth component with EGFR-L858R mutation, and the other was micropapillary component with ALK translocation accompanying mediastinal lymphnode metastases. While he experienced disease recurrence, the disease was controlled by an ALK inhibitor, given based on the findings of surgical specimens. This is the first case who had two simultaneous lung cancers with EGFR mutation and ALK translocation in each respective lesion, and was successfully treated with ALK inhibitor at the post-surgical recurrence. J. Med. Invest. 64: 305-307, August, 2017.

Obstructive bronchiolitis (OB) is an intractable disease causing stenosis in the surrounding bronchiolar region and bronchiolar lumen obstruction. Causes of OB are lung and hematopoietic stem-cell transplantation, collagen diseases, infections, and foods, but there are very few reports of drug-induced OB [1]. Imatinib is a drug used for the treatment of leukemia, gastrointestinal stromal tumors, etc. Although there are some reports of imatinib-induced lung injury as a complication (Ohnishi et al., 2006; Ma et al., 2003; Yamasawa et al., 2008; Koide et al., 2011) [[2], [3], [4], [5]], OB has not been reported. We have encountered a patient with OB related to imatinib administered for chronic myelogenous leukemia, who we have followed for 10 years. Drug-induced OB is very rare, but our case demonstrates the importance of considering the possibility of airway lesions by evaluating pulmonary function and expiratory computed tomography in patients with respiratory symptoms despite no shading on imaging.

Background Most patients with combined pulmonary fibrosis and emphysema (CPFE) are males, and heavy smokers. CPFE is more prevalent than fibrosis in patients with lung cancer, and patients with CPFE usually have a poor prognosis. This study reviewed the differences in the prevalence of lung cancer among patients with normal, fibrosis, emphysema and CPFE via chest computed tomography (CT), and the relationship between histopathology and the localizations of lung cancer. Methods Patients that were diagnosed with lung cancer confirmed by pathological examinations between 2003 and 2011 were retrospectively reviewed to obtain clinical, pathological, and radiological data. These patients were categorized into four groups based on chest CT findings: normal, fibrosis, emphysema and CPFE. Results Two hundred and seventy-four patients with lung cancer were classified into 146 normal, 14 fibrosis, 78 emphysema, and 36 CPFE groups. Combined centriacinar and paraseptal emphysema was common in the CPFE group. The prevalence of squamous cell carcinoma in the CPFE group was significantly higher in comparison to the normal group. The rate of peripheral localization of lung cancer in the CPFE group was significantly higher in comparison to the normal, fibrosis, and emphysema groups. The prevalence of squamous cell carcinoma of peripheral areas in the CPFE group was significantly higher in the normal and emphysema groups. Conclusions CPFE patients demonstrated histopathological and radiological differences concerning the histological types and localization of lung cancers.

Summary Background The diagnosis of pulmonary aspergillosis is difficult because the sensitivity of the conventional methods for the detection of Aspergillus such as culture and cytology, is poor. To improve the sensitivity for Aspergillus detection, the detection of galactomannan antigen has been investigated. The serum galactomannan (GM) antigen has been recognized to be a useful tool for the diagnosis of invasive pulmonary aspergillosis. However, the utility of the galactomannan antigen for the diagnosis of pulmonary aspergillosis other than invasive pulmonary aspergillosis (IPA) has been unclear. Methods The GM antigen using serum and bronchial washing (BW) using bronchofiberscopy for the diagnosis of pulmonary aspergillosis other than IPA were measured. Results In 45 enrolled patients, 7 patients had pulmonary aspergillosis, 5 of these patients had chronic necrotizing pulmonary aspergillosis and 2 patients had allergic bronchopulmonary aspergillosis. The area under the receiver operating characteristic (ROC) curve was 0.89 for the BW GM antigen detection test, and 0.41 for the serum GM antigen detection test, suggesting that the BW GM antigen detection test exhibits a better diagnostic performance than the serum GM antigen detection test. The BW GM antigen detection test had a sensitivity of 85.7% and a specificity of 76.3% at a cut-off level of ≥0.5, which was the optimal cut-off level obtained by the ROC curve. Conclusion The BW GM antigen detection test is thought to be a promising test for the diagnosis of pulmonary aspergillosis other than IPA.

BACKGROUND: Several promising molecular-targeted drugs are used for advanced renal cancers. However, complete remission is rarely achieved, because none of the drugs targets a key molecule that is specific to the cancer, or is associated with “oncogene addiction” (dependence on one or a few oncogenes for cell survival) of renal cancer. Recently, an anaplastic lymphoma kinase (ALK) fusion, vinculin-ALK, has been reported in pediatric renal cell carcinoma (RCC) cases who have a history of sickle cell trait. In this context, ALK inhibitor therapy would constitute a therapeutic advance, as has previously been demonstrated with lung cancer, inflammatory myofibroblastic tumors, and anaplastic large cell lymphomas. METHODS: Anti-ALK immunohistochemistry was used to screen 355 tumor tissues, using the intercalated antibody-enhanced polymer (iAEP) method. The cohort consisted of 255 clear cell RCCs, 32 papillary RCCs, 34 chromophobe RCCs, 6 collecting duct carcinomas, 10 unclassified RCCs, 6 sarcomatoid RCCs, and 12 other tumors. RESULTS: Two patients (36- and 53-year-old females) were positive for ALK as determined by iAEP immunohistochemistry. Using 5′- rapid amplification of complementary DNA ends, we detected TPM3-ALK and EML4-ALK in these tumors. The results of this study were confirmed by fluorescence in situ hybridization assays. The 2 ALK-positive RCCs were unclassified (mixed features of papillary, mucinous cribriform, and solid patterns with rhabdoid cells) and papillary subtype. They comprised 2.3% of non–clear cell RCCs (2 of 88) and 3.7% of non–clear cell and nonchromophobe RCCs (2 of 54). CONCLUSIONS: The results of this study indicate that ALK fusions also exist in adult RCC cases without uncommon backgrounds. These findings confirm the potential of ALK inhibitor therapy for selected cases of RCC. Cancer 2012. © 2012 American Cancer Society.

A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and she was diagnosed to have acute eosinophilic pneumonia (AEP). The cause was thought to be cigarette smoking, because she had started smoking just before the development of AEP and her condition improved after cigarette smoking cessation, without corticosteroid treatment. The cytokines which are thought to be involved in eosinophilic accumulation in the lungs were analyzed using bronchoalveolar lavage fluid (BALF) and serum. Of the analyzed cytokines, only regulated on activation, normal T cell expressed and secreted (RANTES) increased in the serum after the improvement. RANTES is a unique chemokine which attracts not only eosinophils, but also T cells. Interestingly, in this case, the eosinophil count in the blood increased in parallel with the lymphocyte count after the improvement. These findings are interesting because it may help to understand the pathogenesis of AEP and the role of RANTES.

Purpose: EML4-ALK is a transforming fusion tyrosine kinase, several isoforms of which have been identified in lung cancer. Immunohistochemical detection of EML4-ALK has proved difficult, however, likely as a result of low transcriptional activity conferred by the promoter-enhancer region of EML4. The sensitivity of EML4-ALK detection by immunohistochemistry should be increased adequately. Experimental Design: We developed an intercalated antibody-enhanced polymer (iAEP) method that incorporates an intercalating antibody between the primary antibody to ALK and the dextran polymer-based detection reagents. Results: Our iAEP method discriminated between tumors positive or negative for EML4-ALK in a test set of specimens. Four tumors were also found to be positive for ALK in an archive of lung adenocarcinoma (n = 130) and another 4 among fresh cases analyzed in a diagnostic laboratory. These 8 tumors were found to include 1 with EML4-ALK variant 1, 1 with variant 2, 3 with variant 3, and 2 with previously unidentified variants (designated variants 6 and 7). Inverse reverse transcription-PCR analysis revealed that the remaining tumor harbored a novel fusion in which intron 24 of KIF5B was ligated to intron 19 of ALK. Multiplex reverse transcription-PCR analysis of additional archival tumor specimens identified another case of lung adenocarcinoma positive for KIF5B-ALK. Conclusions: The iAEP method should prove suitable for immunohistochemical screening of tumors positive for ALK or ALK fusion proteins among pathologic archives. Coupling of PCR-based detection to the iAEP method should further facilitate the rapid identification of novel ALK fusion genes such as KIF5B-ALK.

A 32 year-old woman with bilateral hilar lymphadenopathy suffered from syncopal attacks after her first delivery. Electrocardiograms showed complete atrioventricular block (AVB) and myocardial scintigrams demonstrated a decreased uptake in the anteroseptal area. She was diagnosed as having postpartal cardiac acceleration of sarcoidosis. Because she rejected permanent pacemaker implantation, we started steroid therapy under temporary pacing. Fortunately, the treatment was very effective. Even after tapering-off of the steroid, the AVB has never reappeared. Permanent pacemaker implantation with subsequent steroid therapy is generally recommended for complete AVB due to cardiac sarcoidosis. However, steroid therapy alone can be considered for some selected cases.

A computational model of a car driver's cognitive process was developed to create more useful assistance technology for making driving safer. The model's status is mainly determined by the driver's eye movement. In this model, we defined two types of risk : explicit risk for visible objects and inexplicit risk for non-visible areas. In our simulation, we attempted to reconstruct the driver's eye movement while driving using our model.

Background Outcomes of patients with lung adenocarcinomas can be predicted to some extent from the pathologic stage (p-stage). Although all attempts are made to fully remove cancer lesions, still a number of p-stage I patients without metastatic disease at the time of surgery develop recurrences and die of cancer. It is thus very important to identify p-stage I patients who are at risk of recurrence. Methods Previously, using microdissected samples, we identified metastasis-related genes. Using real-time reverse-transcriptase polymerase chain reaction analysis, we investigated the transcriptional levels of the top metastasis-related genes using 96 independent test lung adenocarcinoma samples and investigated their correlations with the prognosis. Results and Conclusions We document evidence that p-stage I patients with HOXB2 up-regulation have a worse prognosis than those with HOXB2 down-regulation ( p = 0.0065), whereas the HOXB2 status has no prognostic significance for p-stage II–IV patients. Comparing tumors and corresponding normal lung tissue, we confirmed HOXB2 up-regulated lesions to have much higher HOXB2 expression than the corresponding normal tissue. Confirmation with a larger number of samples is needed, with further research to clarify the molecular functions of HOXB2.

Obstructive Sleep Apnea-hypopnea Syndrome Patients with Overweight and Hypertension in a Japanese Workplace: Ken OKABAYASHI, et al. JR East Health Promotion Center, East Japan Railway Company—The objective of this study was to determine the relationship between obstructive sleep apnea-hypopnea syndrome (OSAHS) and overweight combined with hypertension and to examine whether OSAHS in conjunction with overweight and hypertension is associated with daytime sleepiness. In a Japanese workplace of 28,636 employees, 368 men (19-62 yr old), who were anxious regarding their OSAHS symptoms, underwent home pulse oximetry. Of these, 153 men subsequently underwent all-night polysomnography (PSG), and OSAHS was diagnosed in 149. We next classified these 149 men into the following groups: A (Overweight (-)/Hypertension (-), n=41), B (Overweight (-)/ Hypertension (+), n=15), C (Overweight (+)/ Hypertension (-), n=46), and D (Overweight (+)/ Hypertension (+), n=47). The Epworth Sleepiness Scale (ESS) was used to evaluate daytime sleepiness and the apnea-hypopnea index (AHI) was used to evaluate the severity of OSAHS. The averages of the ESS score and the AHI were compared in each group. Both the average ESS scores and the percentage of ESS scores ≥11 were not significantly different among the groups. The average AHI of group D was the highest among all of the groups and that of group C was significantly higher than those of groups A and B. In all the groups, the OSAHS patients with overweight and hypertension in this study had the highest AHI. The level of daytime sleepiness evaluated by the ESS in this study was almost the same in the OSAHS patients regardless of the degree of overweight or hypertension. These observations suggest that it is necessary to positively recommend PSG to men who are suspected of having OSAHS with overweight and hypertension, even if they do not have daytime sleepiness. (J Occup Health 2007; 49: 117-124)

Modeling of human cognitive process is one of important research field for computational intelligence. In this study, we try to construct a computational model of car driver that can explain real world driver behavior. Through the research, we try to establish foundation for a bridge between basic science and engineering requirement. In our previous work, we proposed a model of driver's eye movements that consists of bottom-up and top-down eye motion sub models. This paper proposes an extended version of the previous eye motion model. In the current extended model, top-down eye motion is determined based on the driver's driving plan, whereas the bottom-up eye motion is determined based on predicted locations of moving objects