Atsuhito Ushiki

Genetic Heterogeneity of EGFR Mutation in Pleomorphic Carcinoma of the Lung: Response to Gefitinib and Clinical Outcome

Somatic epidermal growth factor receptor (EGFR) mutations in exons 19 and 21 have been found in non-small cell lung cancer (NSCLC) and are associated with the therapeutic response to gefitinib in patients with advanced NSCLC. We report a case of pleomorphic carcinoma of the lung with different EGFR mutations. Prior to gefitinib treatment, an exon 19 deletion of EGFR mutation was positive in the specimens obtained from pleural effusion and left cervical lymph node, histologically proven to be adenocarcinoma. However, the response to gefitinib was poor and the patient died of progressive disease 4 months after the initiation of gefitinib therapy. Postmortem examination revealed the major histological component to be of the sarcomatoid or pleomorphic type with scant mixed adenocarcinoma, resulting in a histological diagnosis of pleomorphic carcinoma of the lung. Although the adenocarcinomatous tissue was still positive for exon 19 deletion of EGFR mutation alone, sarcomatous components had both the exons 19 deletion and 20 T790M mutation concomitantly, thought to be a gefitinib resistance mutation. Pulmonary pleomorphic carcinoma is a rare NSCLC composed of biphasic and heterogeneous malignant cell populations. The present case suggested that expression of different EGFR mutations is related to the biphasic histological appearance in pulmonary pleomorphic carcinoma.

Viral infections in patients with an acute exacerbation of idiopathic interstitial pneumonia.

Abstract Background Patients with slowly progressive idiopathic interstitial pneumonia, including idiopathic pulmonary fibrosis, often deteriorate, thus suggesting that the clinical course may be unpredictable. Such episodes are termed acute exacerbation of idiopathic interstitial pneumonia. The etiology of an acute exacerbation of idiopathic interstitial pneumonia is unknown. In this study, we tested the hypothesis that an acute exacerbation of idiopathic interstitial pneumonia is induced by respiratory viral infections. Methods Bronchoalveolar lavage fluid obtained from patients with an acute exacerbation of idiopathic interstitial pneumonia was tested for viral nucleic acid using polymerase chain reaction. Results Only 1 of the 14 patients with an acute exacerbation of idiopathic interstitial pneumonia exhibited evidence of respiratory syncytial virus B, and 2 patients exhibited evidence of cytomegalovirus. Seven patients fulfilled the diagnostic criteria of idiopathic pulmonary fibrosis. Conclusions Most cases with an acute exacerbation of idiopathic interstitial pneumonia are not caused by a viral infection.

Comparison of gene expression profiling between lung fibrotic and emphysematous tissues sampled from patients with combined pulmonary fibrosis and emphysema

BackgroundCombined pulmonary fibrosis and emphysema (CPFE) is characterized by both emphysema of the upper zone and diffuse parenchymal lung disease with fibrosis of the lower zone of the lung on chest computed tomography. The aim of this study was to investigate the mechanism of CPFE regarding gene expressions by comparing the results of microarray sequences between fibrotic and emphysematous lesions in the lungs of CPFE patients.ResultsThe expression profiles of the fibrotic and emphysematous lesions were remarkably different in terms of function. Genes related to the immune system, structural constituents of the cytoskeleton, and cellular adhesion were overexpressed in fibrotic lesions, while genes associated with the cellular fraction, cell membrane structures, vascular growth and biology, second-messenger-mediated signaling, and lung development (all processes that contribute to the destruction and repair of cells, vessels, and the lung) were overexpressed in emphysematous lesions.ConclusionsThe differences in gene expression were detected in fibrotic and emphysematous lesions in CPFE patients. We propose that the development of coexisting fibrotic and emphysematous lesions in CPFE is implemented by these different patterns of gene expressions.

l-Carbocisteine reduces neutrophil elastase-induced mucin production

Human neutrophil elastase (HNE) exists in high concentrations in airway secretions and produces mucus hypersecretion in patients with chronic obstructive pulmonary disease (COPD). L-carbocisteine improves the quality of life and reduces exacerbation in COPD patients. However the precise mechanism is uncertain. We examined the effects of L-carbocisteine on HNE-induced mucus hypersecretion and on the production of reactive oxygen species (ROS) which is associated with mucin production induced by HNE. NCI-H292, a human lung mucoepidermoid carcinoma cell line, was treated with or without HNE and L-carbocisteine. MUC5AC mRNA expression and ROS production in the cells, and MUC5AC protein concentration in supernatants were measured. HNE increased MUC5AC mRNA expression and MUC5AC protein concentration in supernatants in the cells. L-carbocisteine reduces HNE-induced mRNA expression and protein secretion of MUC5AC. L-carbocisteine also reduced ROS production in the cells induced by HNE. Reduction of HNE-induced mucus secretion by L-carbocisteine in the pulmonary epithelial cells may partly relate to the reduction of ROS.

Superior mesenteric artery syndrome following initiation of cisplatin-containing chemotherapy: a case report

IntroductionSuperior mesenteric artery syndrome is a rare cause of upper intestinal obstruction resulting from compression of the duodenum by the superior mesenteric artery and abdominal aorta.Case presentationWe describe a case of superior mesenteric artery syndrome in a 61-year-old Japanese man with non-small cell lung cancer who had been treated with cisplatin-containing chemotherapy and had lost 7 kg in weight. The diagnosis was confirmed by the typical findings of abdominal computed tomography showing distended stomach resulting from compression of the third portion of the duodenum and reduction of an aortomesenteric distance and aortomesenteric angle.ConclusionsThis case highlights the importance of considering the possibility of superior mesenteric artery syndrome in patients treated with chemotherapy, especially those presenting with a low body mass index and showing weight loss during chemotherapy.

Cytokine profiles in the BAL fluid of IgG4-related respiratory disease compared with sarcoidosis

IgG4-related disease (IgG4-RD) is a multiorgan disorder that involves the salivary glands, pancreas and lungs [1]. We previously reported six patients with autoimmune pancreatitis (AIP) who showed characteristic central airway stenosis and bilateral hilar lymphadenopathy (BHL) that mimics sarcoidosis [2, 3]. We subsequently prospectively identified four additional patients with AIP and one patient with IgG4-related kidney disease (IgG4-RKD) with similar chest computed tomography (CT) findings and IgG4-positive plasma cell infiltration without granuloma in the airways. 10 out of 11 patients were diagnosed with AIP by their gastroenterologists based on the diagnostic AIP criteria proposed by the Japanese Pancreatic Society in 2011 [4] and the remaining one patient was diagnosed with IgG4-RKD by renal physicians based on the renal biopsy specimens in our hospital. All the 11 patients showed BHL and bronchial wall thickening on chest CT and were underwent transbronchial lung biopsy and bronchial biopsy according to our routine protocol [3]. The median IgG4-positive cell count and the percentage of IgG4-positive cells to IgG-positive plasma cells was 54.3 (range 17–80.6) per high-power field and 63.6% (range 34.5–96.5%), respectively. Thus, we diagnosed the 11 patients with IgG4-related respiratory disease (IgG4-RRD) characterised by airway involvement and BHL at multidisciplinary meetings of our hospital, as previously reported [3]. None of the 11 patients had oxygen desaturation and seven out of 11 patients had cough. The 10 patients with AIP showed one or more extrapulmonary manifestations other than in the pancreas and the one patient with IgG4-RKD had submandibular involvement. Nine patients with AIP received oral corticosteroid therapy for pancreatic lesions, whereas one patient did not because of the presence of severe cataract and glaucoma. The patient with IgG4-RKD did not receive oral corticosteroid therapy because spontaneous improvement of renal function was observed. Two patients received inhaled steroid therapy for cough. All 11 patients were alive at the end of our study and had no respiratory symptoms from these therapies. BAL cytokines of IgG4-RRD patients are more characteristic of the Th2 response than those of sarcoidosis patients http://ow.ly/T2gDV

An AIDS patient with immune reconstitution inflammatory syndrome due to pulmonary Mycobacterium kansasii infection during antiretroviral therapy

After the recovery of pneumocystis pneumonia, amebiasis, and cytomegalovirus duodenal ulcer in a patient with AIDS, antiretroviral therapy was initiated. Fever was first noted on the 11th day of administration of the highly active antiretroviral therapy (HAART), and chest radiography showed infiltration into the right lower lobe of the lung on the 19th day. Bronchoscopy was performed, with a tentative diagnosis of pulmonary tuberculosis, but Mycobacterium kansasii was eventually identified. M. kansasii may also be a pathogenic organism causing immune reconstitution inflammatory syndrome.

Two patients with TAFRO syndrome exhibiting strikingly similar anterior mediastinal lesions with predominantly fat attenuation on chest computed tomography

We herein report on two middle-aged men with TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis or renal failure, and organomegaly) syndrome, a unique clinicopathological variant of multicentric Castleman׳s disease recently proposed in Japan. Strikingly similar anterior mediastinal fat swellings with soft tissue density were observed in the patients on chest computed tomography. In TAFRO syndrome, bilateral pleural effusion and slight lymph node swelling are common in the thoracic region; however, anterior mediastinal lesions have not been previously observed. Although the mechanisms of anterior mediastinal lesions have not been defined, these lesions seem to have a close relationship with TAFRO syndrome.

Computed tomography-guided bronchoscopy in the diagnosis of small peripheral pulmonary lesions: A retrospective study of 240 examinations in a single academic center

BACKGROUND Factors that affect the diagnostic yield in computed tomography (CT)-guided bronchoscopy have not yet been fully evaluated. To improve the diagnostic yield of peripheral pulmonary lesions (PPLs) by CT-guided bronchoscopy, we quantitatively analyzed factors affecting the diagnostic yield. METHODS The data were collected for 240 PPLs in 237 patients examined by using CT-guided bronchoscopy between October 2003 and November 2011 in our respiratory center. The association of diagnostic yield with the CT bronchus sign (CT-BS), lesion size, location, number of tissue specimens, and type of bronchoscope was retrospectively assessed. RESULTS The diagnostic yield of PPLs with negative CT-BS was significantly lower (2.9%) than that for PPLs with positive CT-BS (52.2%; p<0.01). Among the PPLs with positive CT-BS, the yield was significantly higher in those in the left S(3) than for lesions in other bronchial segments (83.3% vs. 50.3%; p<0.05). Lesion size was not significantly associated with diagnostic yield. The yield was significantly lower in PPLs without lung tissue specimens than in lesions with biopsy specimens (p<0.01). Moreover, a thin bronchoscope produced a higher yield in comparison with other bronchoscope types (66.0% vs. 47.6%; p<0.05). Multivariate analysis revealed that the number of biopsy specimens was an independent factor affecting diagnostic yield. CONCLUSIONS CT-guided bronchoscopy is valuable in the diagnosis of PPLs with positive CT-BS regardless of lesion size; however, PPLs with negative CT-BS are not good candidates for CT-guided bronchoscopy. Obtaining tissue specimens by biopsy is a critical factor in diagnosing PPLs.

Virtual bronchoscopic navigation as an aid to CT-guided transbronchial biopsy improves the diagnostic yield for small peripheral pulmonary lesions: Diagnostic yield with VBN and CT-TBB

Virtual bronchoscopic navigation (VBN) entails the provision of a virtual display of the bronchial routes that lead to small peripheral pulmonary lesions (PPL). It has been predicted that a combination of computed tomography (CT)‐guided transbronchial biopsy (CT‐TBB) with VBN might improve the diagnostic yield for small PPL. This study sought to investigate that prediction.