Yukihiro Umeda

Pathophysiologic Correlation Between 62Cu-ATSM and 18F-FDG in Lung Cancer

The purpose of this study was to delineate the differences in intratumoral uptake and tracer distribution of 62Cu-diacetyl-bis(N4-methylthiosemicarbazone) (62Cu-ATSM), a well-known hypoxic imaging tracer, and 18F-FDG in patients with lung cancer of pathohistologically different types. Methods: Eight patients with squamous cell carcinoma (SCC) and 5 with adenocarcinoma underwent 62Cu-ATSM and 18F-FDG PET within a 1-wk interval. For 62Cu-ATSM PET, 10-min static data acquisition was started at 10 min after a 370- to 740-MBq tracer injection. After image reconstruction, 62Cu-ATSM and 18F-FDG images were coregistered, and multiple small regions of interest were drawn on tumor lesions of the 2 images to obtain standardized uptake values (SUVs). The regression lines were determined between SUVs for 62Cu-ATSM and 18F-FDG in each tumor. The slope values were compared between SCC and adenocarcinoma to observe pathohistologic differences in intratumoral distribution of the tracers. Results: SUVs for 62Cu-ATSM were lower than those for 18F-FDG in both SCC and adenocarcinoma. SCC tumors showed high 62Cu-ATSM and low 18F-FDG uptakes in the peripheral region of tumors but low 62Cu-ATSM and high 18F-FDG uptakes toward the center (spatial mismatching). The relationship of SUVs for the 2 tracers was negatively correlated with a mean regression slope of −0.07 ± 0.05. On the other hand, adenocarcinoma tumors had a spatially similar distribution of 62Cu-ATSM and 18F-FDG, with positive regression slopes averaging 0.24 ± 0.13. The regression slopes for 62Cu-ATSM and 18F-FDG differed significantly between SCC and adenocarcinoma (P < 0.001). Conclusion: The intratumoral distribution patterns of 62Cu-ATSM and 18F-FDG were different between SCC and adenocarcinoma in lung cancers, indicating that intratumoral regions of high glucose metabolism and hypoxia could differ with the pathohistologic type of lung cancer. The identification of regional biologic characteristics in tumors such as hypoxia, energy metabolism, and proliferation could play a significant role in the clinical diagnosis and therapy planning for non–small cell lung cancer patients.

Prognostic value of dual‐time‐point 18F‐fluorodeoxyglucose positron emission tomography in patients with pulmonary sarcoidosis

Background and objective:  The value of dual‐time‐ point 18F‐FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis.

Hypoxia regulates human lung fibroblast proliferation via p53-dependent and -independent pathways

BackgroundHypoxia induces the proliferation of lung fibroblasts in vivo and in vitro. However, the subcellular interactions between hypoxia and expression of tumor suppressor p53 and cyclin-dependent kinase inhibitors p21 and p27 remain unclear.MethodsNormal human lung fibroblasts (NHLF) were cultured in a hypoxic chamber or exposed to desferroxamine (DFX). DNA synthesis was measured using bromodeoxyuridine incorporation, and expression of p53, p21 and p27 was measured using real-time RT-PCR and Western blot analysis.ResultsDNA synthesis was increased by moderate hypoxia (2% oxygen) but was decreased by severe hypoxia (0.1% oxygen) and DFX. Moderate hypoxia decreased p21 synthesis without affecting p53 synthesis, whereas severe hypoxia and DFX increased synthesis of both p21 and p53. p27 protein expression was decreased by severe hypoxia and DFX. Gene silencing of p21 and p27 promoted DNA synthesis at ambient oxygen concentrations. p21 and p53 gene silencing lessened the decrease in DNA synthesis due to severe hypoxia or DFX exposure. p21 gene silencing prevented increased DNA synthesis in moderate hypoxia. p27 protein expression was significantly increased by p53 gene silencing, and was decreased by wild-type p53 gene transfection.ConclusionThese results indicate that in NHLF, severe hypoxia leads to cell cycle arrest via the p53-p21 pathway, but that moderate hypoxia enhances cell proliferation via the p21 pathway in a p53-independent manner. In addition, our results suggest that p27 may be involved in compensating for p53 in cultured NHLF proliferation.

Imaging the early response to chemotherapy in advanced lung cancer with diffusion‐weighted magnetic resonance imaging compared to fluorine‐18 fluorodeoxyglucose positron emission tomography and computed tomography

To evaluate the feasibility of diffusion‐weighted magnetic resonance imaging (DW‐MRI) for assessment of the early response to chemotherapy and outcome in patients with advanced lung cancer through comparison with fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) and computed tomography (CT).

Multi-arterial infusion chemotherapy for non-small cell lung carcinoma—Significance of detecting feeding arteries and tumor staining

The present study examines the significance of defining feeding arteries to arterial infusion chemotherapy for patients with non-small cell lung carcinoma. We retrospectively studied feeding arteries and findings from 32 patients treated by arterial infusion chemotherapy. We graded tumor staining by angiography and compared grade in the bronchial artery with that of total staining in all detected feeding arteries, and investigated the relationship between grade and treatment response. One patient achieved a complete response and 16 achieved a partial response with no serious adverse effects. Many feeding arteries were detected and the grade of total tumor staining in these patients was significantly higher than that of tumor staining in the bronchial artery. The number of lesions that responded was significantly increased among those with a higher grade of total tumor staining. Precise definition of feeding arteries and sufficient tumor staining are vital to ensure a successful outcome of arterial infusion chemotherapy for patients with NSCLC.

Small airway disease associated with Sjogren's syndrome: Clinico-pathological correlations

BACKGROUND Relationships among clinical, physiological, imaging and pathological findings of small airway disease associated with Sjögrens syndrome have remained unclear. SUBJECTS AND METHODS We retrospectively studied 14 patients who underwent surgical lung biopsy and who were diagnosed with small airway disease associated with primary or secondary Sjögrens syndrome. We compared clinical, bronchoalveolar lavage, physiological, imaging and pathological findings between primary and secondary Sjögrens syndrome. We scored HRCT and pathological abnormalities and investigated correlations among physiological, HRCT and pathological data, changes in physiological parameters and in HRCT scores after two years of treatment, as well as correlations between these values and pathological scores. RESULTS Bronchoalveolar lavage fluid, physiological, imaging and pathological findings of the airways did not significantly differ between primary and secondary Sjögrens syndrome. Air trapping on HRCT negatively correlated with MEF50 and MEF25. Although lymphoid cell infiltration and peribronchiolar fibrosis were the most common pathologies, constrictive change scores correlated negatively with MEF50 and MEF25, positively with air trapping scores and negatively with improvements after therapy in MEF(50), MEF(25) and air trapping. CONCLUSIONS Constrictive change was the most significant determinant of physiological and imaging presentations and of changes in these factors after therapy for small airway disease associated with Sjögrens syndrome.

Prognostic Value of Dual-Time-Point 18F-FDG PET for Idiopathic Pulmonary Fibrosis

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

The effects of concomitant gerD, dyspepsia, and rhinosinusitis on asthma symptoms and FenO in asthmatic patients taking controller medications

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

Blunted Activation of Rho-Kinase in Yak Pulmonary Circulation

Yaks have adapted to high altitude and they do not develop hypoxic pulmonary hypertension. Although we previously identified the important role of augmented nitric oxide synthase activity in the yak pulmonary circulatory system, evidence of the direct involvement of Rho-kinase as a basal vascular tone regulator is lacking. Four domesticated male pure-bred yaks and four bulls that were born and raised at an altitude of 3000 m in the Tien-Shan mountains were studied at an altitude of 3,100 m. Mean pulmonary artery pressure (mPAP) was measured before and after fasudil (60 mg in 20 mL of saline) was intravenously administered using a Swan-Ganz catheter at a rate of 3.3 mL/min for 30 min. Fasudil decreased mPAP in bulls from 67.8±14.9 to 32.3±5.3 mmHg (P < 0.05) after 15 min and the level was maintained for 30 min, but it merely blunted mPAP in yaks from 28.2±4.5 to 25.1±11.1 and 23.2±2.7 mmHg after 5 and 30 min, respectively. These findings comprise the first evidence of a modest role of Rho-kinase in the maintenance of pulmonary artery pressure in the yak.

Osteogenesis Imperfecta Associated with Dendriform Pulmonary Ossification

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