Hirokazu Tokuyasu

Functional assay of NF-κB translocation into nuclei by laser scanning cytometry: inhibitory effect by dexamethasone or theophylline

Abstract Nuclear factor-κ B (NF-κB)/Rel transcription factors play an important role in the inducible regulation of a variety of cytokine genes in epithelial cells. We assessed accumulation of fluorescence-stained NF-κB into propi-dium iodide-stained nuclei using laser scanning cytometry. “Activity-specific” antibodies to the Rel A (p65) and NF-κB1 (p50) subunits of NF-κB were detected in the nuclei of A549 cells (an immortalized human type II alveolar epithelial cell line). Exposure to TNF-alpha caused p65 and p50 to translocate into nuclei in a dose- and time-dependent manner. Preincubation with dexamethasone for 24 h or 30 min, or with theophylline for 30 min before TNF-alpha stimulation attenuated the nuclear translocation of Rel A and p50. These findings suggest that theophylline, as well as dexamethasone, may inhibit translocation of NF-κB.

Lung adenocarcinomas with micropapillary components

PurposeMicropapillary adenocarcinoma is becoming increasingly recognized as a prognostically important histological subtype of carcinoma in various organs. This report presents the clinicopathological findings of lung adenocarcinomas with micropapillary components.MethodsA total of 15 patients with micropapillary components were selected between April 2005 and December 2008. The results of their clinical presentation, metastasis to lymph nodes, pleural invasion, pathological stage, and clinical outcomes were evaluated.ResultsIn all, 12 patients underwent a lobectomy or bilobectomy with a regional lymph node dissection; 8 showed metastases to the regional lymph nodes at the time of the operation. Altogether, 14 of 15 cases showed lymphovascular invasion; 10 cases were up-staged after the operation because of lymph node metastases or pleural invasion. The duration of follow-up ranged from 1 to 42 months (median 16 months). Seven patients are alive without disease, whereas seven are alive with disease and one patient died of disease.ConclusionThese results suggest that the micropapillary components are a manifestation of aggressive behavior, as shown by the frequent lymph node metastases and pleural invasion. Surgeons should search more carefully for metastases and conduct a closer follow-up on these patients when this feature is present with lung adenocarcinoma.

Primary malignant melanoma of the lung with rapid progression

This report presents a case of primary malignant melanoma of the lung with rapid progression in a 68-year-old man. During a regular checkup, a chest roentgenogram revealed an abnormal shadow in the left lower lung field. Computed tomography (CT) of the chest revealed an ill-defined tumor shadow measuring 4 × 3 cm in the left upper lobe. A CT-guided lung biopsy suggested a large-cell carcinoma, and left upper lobectomy was performed. Histopathologically, the tumor was comprised of malignant epithelial tumor cells with large amounts of acidophilic cytoplasm and prominent nuclei. A dark brown pigment was observed in the tumor cells. Immunohistochemical staining was positive for S-100 protein and HMB45; staining for cytokeratin, CAM5.2, and chromogranin was negative. The final diagnosis was malignant melanoma of the lung. Two months later, multiple brain metastases developed, and he died of the disease 6 months after the surgery.

Bilateral multiple sclerosing hemangiomas of the lung

This report presents a case of bilateral multiple sclerosing hemangiomas of the lung in a 73-year-old woman. A computed tomography (CT) scan of the chest showed a total of three well-defined small nodules in the right and left lower lobes of the lung. Because malignant metastatic lung tumors were highly suspected, a wedge resection of the left lower lobe was performed to obtain a definitive diagnosis. Histopathologically, two tumors of the left lower lobe were composed of epithelial-like cuboidal cells covering the surface of papillary protrusions and sheets of round to polygonal cells underneath the epithelial-like cells. The final diagnosis was that both tumors were sclerosing hemangiomas. After surgery the residual lesion of the right lower lobe was carefully followed by chest CT. The size of the right lung nodule did not change over the course of 9 years, and no new lesion has emerged.

Effects on asthma and induction of interleukin-8 caused by Asian dust particles collected in western Japan.

Abstract Objective: Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity. Methods: The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure. Results: Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS. Conclusion: Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.

The maximum standardized 18F-fluorodeoxyglucose uptake on positron emission tomography predicts lymph node metastasis and invasiveness in clinical stage IA non-small cell lung cancer

In patients with clinical stage IA non-small cell lung cancer (NSCLC), we investigated whether the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) by the tumor correlated with lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells, and pleural invasion. From April 2005 to November 2008, 58 patients underwent a lobectomy with systematic hilar and mediastinal lymph node dissection for clinical stage IA NSCLC. All patients had integrated FDG-positron emission tomography (PET)/computed tomography (CT) performed in our center as part of the preoperative workup within one month of resection. The relationships between the SUVmax and pathologic results of lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells, and pleural invasion were examined. Compared with tumors with an SUVmax < or = 2.0, tumors with an SUVmax>2.0 had more frequent lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells and pleural invasion (all P<0.05). Our results suggest that in patients with clinical stage IA NSCLC, SUVmax is an important predictor of tumor invasiveness.

Environmental tobacco smoke and its effect on the symptoms and medication in children with asthma

Environmental tobacco smoke (ETS) worsens asthmatic symptoms. We analyzed the relationship between levels of ETS and asthmatic symptoms and medication. We asked parents of 282 asthmatic children about the general condition, smoke exposure and medication. Patients were classified into three groups: no-ETS (no smoking), mild-ETS (smoking in the house but not in the same room as patient), and heavy-ETS (smoking in the same room as patient). We classified 116 children in no-ETS group, 124 children in mild-ETS group and 42 children in heavy-ETS group. The symptoms were worst and prevalence of leukotriene receptor antagonist and long-acting β2-agonist use were highest in heavy-ETS group. However, there was no statistical difference between no-ETS and mild-ETS groups in prevalence of anti-asthmatic drug use and symptoms. We conclude that a smoking ban in rooms used by asthmatic children is an easy way to reduce ETS, asthmatic symptoms and the use of anti-asthmatic drugs.

Pulmonary resection for metastases from colorectal carcinoma.

A pulmonary resection of metastatic colorectal carcinoma is an accepted method of treatment. The purpose of this study was to confirm the role of resections for pulmonary metastases from colorectal carcinoma, and to determine the clinical course, outcome, and prognostic factors after surgery. A retrospective analysis was conducted of the records of all patients with pulmonary metastases from colorectal carcinoma who underwent a surgical resection between 1995 and 2008, at a single surgical center. The overall 5-year survival rate was 74%. Multivariate Cox analysis demonstrated that the number of pulmonary metastases (HR: 9.40, 95% confidence interval (CI): 1.08-82.2, P=0.0428) and prethoracotomy carcinoembryonic antigen (CEA) level (HR: 9.79, 95% CI: 1.11-86.8, P=0.0404) were statistically significant predictors of survival after the first pulmonary metastasectomy. In addition, a second resection for recurrent metastases was performed in eight patients, and a third resection was done in one patient. There were no major postoperative complications among the patients who underwent second or third resections. Pulmonary resections are considered to be a safe and effective treatment in selective patients.

The maximum standardized uptake values on positron emission tomography to predict the Noguchi classification and invasiveness in clinical stage IA adenocarcinoma measuring 2 cm or less in size

This study investigated whether the standardized uptake value (SUV) of the tumor correlated with the Noguchi classification and tumor invasiveness in patients with clinical stage IA adenocarcinoma < or = 2 cm in size. Fifty-four patients that underwent a curative surgical resection for clinical stage IA adenocarcinoma < or = 2 cm from April 2005 to December 2008 had integrated positron emission tomography (PET)-computed tomography (CT) with 18F-fluorodeoxyglucose (FDG) as part of the preoperative workup. The relationships between the maximum SUV (SUVmax) and Noguchi classification, pathological results of intratumoral lymphatic or vascular invasion of tumor cells, and pleural invasion were examined. In comparison to tumors with an SUVmax>1.0, tumors with an SUVmax < or = 1.0 were more frequently classified as Noguchi type A or B (P<0.0001). Tumors with an SUVmax>1.0 had more intratumoral lymphatic or vascular invasion of tumor cells and pleural invasion (P=0.0005 and P=0.0002). These results suggest that an SUVmax is an important predictor for the Noguchi classification and tumor invasiveness in patients with clinical stage IA adenocarcinoma < or =2 cm in size.

A resected case of solitary pulmonary capillary hemangioma showing pure ground glass opacity.

A 53-year-old Japanese woman was referred to our hospital for pure ground glass opacity (GGO) in the left upper lung on computed tomography. 18F-fluorodeoxyglucose positron emission tomography revealed no abnormal uptake in the lesion. After 4 months of follow-up, we strongly suspected the lesion to be a bronchioloalveolar carcinoma and decided to perform a surgery for diagnosis. Planning to perform lingual segmentectomy by video-assisted thoracic surgery (VATS) with mini thoracotomy, we finally performed the left upper lobectomy to guarantee the optimal margin by VATS, because the lesion was not identified by palpation. Final pathological diagnosis was a solitary pulmonary capillary hemangioma (SPCH). We herein report a resected case of SPCH showing pure GGO and review all reported SPCH cases.