Young Kyung Lee

Quantitatively assessed dynamic contrast-enhanced magnetic resonance imaging in patients with chronic obstructive pulmonary disease: correlation of perfusion parameters with pulmonary function test and quantitative computed tomography.

Objectives:The purpose of this study is to evaluate the correlation of the perfusion parameters of 3-dimensional, contrast-enhanced magnetic resonance (MR) imaging (3D CEMRI) with pulmonary function test (PFT) and quantitative computed tomography (CT) parameters in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods:In 14 patients with COPD, 3D CEMRI was performed. From the signal intensity-time curves, pulmonary blood flow (PBF), pulmonary blood volume (PBV), and mean transit time of each pixel was calculated. From the volumetric CT data, the quantitative parameters including the volume fraction of the lung below −950 Housefield Units (V−950) and mean lung density were assessed. The correlation between the MR perfusion parameters and the parameters from quantitative CT and PFT was assessed using Spearman correlation analysis. The correspondence of the regional impairment of perfusion on MR perfusion maps to the areas of emphysema on quantitative CT maps in each patient was assessed qualitatively using a 4-class visual scoring method by 2 readers. Results:All 3D CEMRI examinations were successfully completed and MR perfusion parameters were obtained in all patients. The Spearman correlation test showed that PBF positively correlated with forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (R = 0.49, P = 0.044), PBV positively correlated with FEV1/FVC (R = 0.69, P = 0.006) and negatively correlated with V−950 (R = −0.61, P = 0.020), and mean transit time positively correlated with FEV1 (R = 0.63, P = 0.017) and FEV1/FVC (R = 0.76, P = 0.002). The areas of perfusion impairment on PBF and PBV maps were relatively well correlated with the areas of emphysema on CT maps [very good or good: PBF 71.5% (reader 1) and 64.3% (reader 2) of the patients, &kgr; = 0.47 (P < 0.001); PBV 78.6% (reader 1) and 78.6% (reader 2) of the patients, &kgr; = 0.89 (P < 0.001)]. Conclusions:This study shows that the deterioration of perfusion parameters measured on MR in patients with COPD, correlates with worsening of airflow limitation on PFT and emphysema index on CT. Regional heterogeneity of emphysema on CT matches with the decreased perfusion on MR.

Responses to inhaled long-acting beta-agonist and corticosteroid according to COPD subtype☆

RATIONALE Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disorder in which a number of different pathological processes lead to recognition of patient subgroups that may have individual characteristics and distinct responses to treatment. OBJECTIVES We tested the hypothesis that responses of lung function to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid might differ among patients with various COPD subtypes. METHODS We classified 165 COPD patients into four subtypes according to the severity of emphysema and airflow obstruction: emphysema-dominant, obstruction-dominant, mild-mixed, and severe-mixed. The emphysema-dominant subtype was defined by an emphysema index on computed tomography of more than 20% and FEV(1) more than 45% of the predicted value. The obstruction-dominant subtype had an emphysema index < or = 20% and FEV(1) < or = 45%, the mild-mixed subtype had an emphysema index < or = 20% and FEV(1) > 45%, and the severe-mixed subtype had an emphysema index > 20% and FEV(1) < or = 45%. Patients were recruited prospectively and treated with 3 months of combined inhalation of long-acting beta-agonist and corticosteroid. RESULTS After 3 months of combined inhalation of long-acting beta-agonist and corticosteroid, obstruction-dominant subtype patients showed a greater FEV(1) increase and more marked dyspnea improvement than did the emphysema-dominant subgroup. The mixed-subtype patients (both subgroups) also showed significant improvement in FEV(1) compared with the emphysema-dominant subgroup. Emphysema-dominant subtype patients showed no improvement in FEV(1) or dyspnea after the 3-month treatment period. CONCLUSION The responses to 3 months of combined inhalation of long-acting beta-agonist and corticosteroid differed according to COPD subtype.

The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC)

We evaluated whether ribonucleotide reductase regulatory subunit M1 (RRM1) protein expression by immunohistochemistry (IHC) is a predictor of survival and response in gemcitabine-treated, advanced non-small cell lung cancer (NSCLC). We retrospectively collected 40 formalin-fixed, paraffin-embedded NSCLC tissues to investigate the protein expression of RRM1 by IHC with a purified rabbit anti-human RRM1 polyclonal antibody (ProteinTech Group, Chicago, IL, USA). RRM1 expression was positive in 14 (35%) and negative in 26 (65%) cases. Ten (25%) patients were treated as first-line and 30 (75%) patients as second-line. The median age was 61 years and M/F was 31/9. Stage IIIB/IV was 7/33 and adenocarcinoma/squamous cell carcinoma/other cell type was 20/16/4. Other characteristics, including age, gender, stage, cell type and first/second-line were not statistically different in the RRM-positive and RRM-negative groups. The overall survival of RRM1-positive groups was significantly shorter than RRM-negative groups (5.1 months vs. 12.9 months, p = 0.022). The response rates of 38 out of 40 patients were assessable. Disease control rate (PR+SD) of the RRM1-positive groups was significantly lower than that of RRM1-negative groups (23% vs. 56%, p = 0.053). In patients with gemcitabine-treated advanced NSCLC, patients with RRM1-positive tumors had worse overall survival and disease control than patients with RRM1-negative tumors.

A study on the incidence of ABL gene deletion on derivative chromosome 9 in chronic myelogenous leukemia by interphase fluorescence in situ hybridization and its association with disease progression.

Fluorescence in situ hybridization for the BCR/ABL rearrangement in 138 bone marrow specimens from 59 Philadelphia+ (Ph+) chronic myelogenous leukemia (CML) patients, 35 Ph+ acute lymphoblastic leukemia (ALL) patients, and 57 Ph− ALL patients was used. Sixteen (27.1%) of the 59 CML patients had deletions of the residual ABL gene on the derivative chromosome 9. During the study period, 32 of the 59 CML patients progressed to blast crisis or accelerated phase. Of these, nine patients had residual ABL gene deletions on the derivative chromosomes 9 and 23 patients had no deletions. The mean duration from first diagnosis to blast crisis or accelerated phase for the nine patients with ABL deletions was 32.8 months, and for the 23 patients without ABL deletions, it was 62.4 months (P = 0.017). The overall survival time for the 16 patients with deletions was 32.8 months, and for the 43 patients without deletions, it was 60.1 months (P = 0.164). ABL deletions were not detected among the 35 ALL patients (17 with major BCR/ABL, 18 with minor BCR/ABL), and it appears that this deletion occurs rarely or not at all in Ph+ ALL patients, which is in contrast to the CML patients (27.1%). However, we detected two ALL cases with ABL deletion but without BCR/ABL rearrangement among 49 Ph− ALL and 66 Ph− AML patients. In conclusion, patients with ABL deletions progress to blast crisis or accelerated phase in a significantly shorter time than do those without such deletions. It is therefore suggested that the ABL deletion is an indicator of a poor prognosis in CML.

Acute and chronic complications of aortic intramural hematoma on follow-up computed tomography: incidence and predictor analysis.

Objective: To ascertain the incidence of acute and chronic complications of aortic intramural hematoma (IMH) and to analyze the predictors of the development of each complication. Materials and Methods: This retrospective study includes 107 consecutive patients diagnosed with aortic IMH by means of computed tomography (CT) during the period from January 1998 to December 2003 and followed up with serial CT examinations (median follow-up period, 320 days). There were 36 patients with type A and 71 with type B IMH. Initial and follow-up CT scans were reviewed, with special attention given to the development of complications, such as increase in the thickness of IMH, clinical and hemodynamic evolution requiring urgent surgery, and development of aortic dissection and/or aneurysm. If each complication developed within 30 days after the initial episode, we classified it as an acute complication; the others were classified as chronic complications. The time interval between the initial and the subsequent CT examination showing each complication was recorded. To identify the predictors of each complication, we analyzed the demographic and CT findings with regard to the following factors: age, sex, maximum thickness of the hematoma, maximum aortic diameter on initial CT examination, ulcerlike projection (ULP) on initial and follow-up CT examinations, and the degree of atherosclerosis. The Cox proportional hazards regression model with stepwise multivariate analyses was used to determine the significant predictors of each complication. Results: Sixteen patients had acute complications consisting of aortic dissection (n = 7), aortic aneurysm (n = 6), and acute clinical and hemodynamic evolution requiring operation (n = 3). Three additional patients with aortic dissection (n = 1) and aneurysm (n = 2) underwent emergency surgery. Twenty-three patients with chronic complications had aortic dissection (n = 3), and aortic aneurysm (n = 20). Cox proportional hazards regression model revealed that the maximal diameter of involved aorta is the only significant predictor of the development of acute complications (P = 0.006), whereas the age (P = 0.040), type A IMH (P = 0.015), presence of ULP (P = 0.015), and newly developed ULP as revealed on follow-up CT examination (P = 0.032) were significant predictors of the development of chronic complications. With regard to the aortic dissection in 10 patients (9.3%; type A/B ratio, 5:5; median time interval, 34 days), Cox proportional hazards regression model revealed that the maximal thickness of the hematoma is the only significant predictor (P = 0.018). Twenty-one saccular and 5 fusiform aneurysms (24.3%) developed, as revealed on follow-up CT examinations (median time interval, 180 days). The presence of ULP (P = 0.030), type A (P = 0.038) and the maximal thickness of the hematoma (P = 0.017) were significant predictors for the development of an aneurysm. Conclusions: The maximum thickness of a hematoma on the initial CT is the significant factor predicting the development of aortic dissection and aortic aneurysm. Patients with type A IMH and ULP, as revealed by initial and short-term follow-up CT examinations, should be carefully followed up with subsequent CT examination to monitor the development of an aortic aneurysm, which is a relatively common chronic complication of IMH.

Feasibility of Automated Quantification of Regional Disease Patterns Depicted on High-Resolution Computed Tomography in Patients with Various Diffuse Lung Diseases

Objective This study was designed to develop an automated system for quantification of various regional disease patterns of diffuse lung diseases as depicted on high-resolution computed tomography (HRCT) and to compare the performance of the automated system with human readers. Materials and Methods A total of 600 circular regions-of-interest (ROIs), 10 pixels in diameter, were utilized. The 600 ROIs comprised 100 ROIs that represented six typical regional patterns (normal, ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). The ROIs were used to train the automated classification system based on the use of a Support Vector Machine classifier and 37 features of texture and shape. The performance of the classification system was tested with a 5-fold cross-validation method. An automated quantification system was developed with a moving ROI in the lung area, which helped classify each pixel into six categories. A total of 92 HRCT images obtained from patients with different diseases were used to validate the quantification system. Two radiologists independently classified lung areas of the same CT images into six patterns using the manual drawing function of dedicated software. Agreement between the automated system and the readers and between the two individual readers was assessed. Results The overall accuracy of the system to classify each disease pattern based on the typical ROIs was 89%. When the quantification results were examined, the average agreement between the system and each radiologist was 52% and 49%, respectively. The agreement between the two radiologists was 67%. Conclusion An automated quantification system for various regional patterns of diffuse interstitial lung diseases can be used for objective and reproducible assessment of disease severity.

Quantitative assessment of change in regional disease patterns on serial HRCT of fibrotic interstitial pneumonia with texture-based automated quantification system

AbstractObjectivesTo evaluate the usefulness of a texture-based automated quantification system (AQS) for evaluating the extent and interval change of regional disease patterns on initial and follow-up high-resolution computed tomographies (HRCTs) of fibrotic interstitial pneumonia (FIP).MethodsEighty-nine patients with clinically and/or biopsy confirmed usual interstitial pneumonia (UIP) (n = 71) and non-specific interstitial pneumonia (NSIP) (n = 18) were included. An AQS to quantify five disease patterns (ground-glass opacity [GGO], reticular opacity [RO], honeycombing [HC], emphysema [EMPH], consolidation [CONS]) and normal lung was developed. The extent and interval changes of each disease pattern, FS (fibrosis score), TA (total abnormal lung fraction) of entire lung on initial and 1-year follow-up HRCTs were quantified. The agreement between the results of AQS and two readers was assessed. Results of AQS were correlated with forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLco).ResultsThe Intraclass correlation coefficient (ICC) study revealed acceptable agreement between visual assessment and AQS (r = 0.78, 0.66 for HC; 0.76, 0.61 for FS; 0.64, 0.68 for TA, initial and follow-up HRCTs, respectively). Linear regression analysis revealed the extent of HC, TA on initial CT, interval changes of FS contributed negatively to DLco, and interval changes of FS, TA contributed negatively to FVC.ConclusionsOur AQS is comparable with visual assessment for evaluating the disease extent and the interval changes of FIP on HRCT.Key Points• HRCT is widely used to assess fibrotic interstitial pneumonia • An automated quantification system matched well with visual assessment of HRCT • Abnormal lung fraction on HRCT correlated with the decrease in diffusion capacity • Automated quantification of HRCT images is useful in assessing fibrotic interstitial pneumonia

Backfitting and smooth backfitting for additive quantile models

In this paper, we study the ordinary backfitting and smooth backfitting as methods of fitting additive quantile models. We show that these backfitting quantile estimators are asymptotically equivalent to the corresponding backfitting estimators of the additive components in a specially-designed additive mean regression model. This implies that the theoretical properties of the backfitting quantile estimators are not unlike those of backfitting mean regression estimators. We also assess the finite sample properties of the two backfitting quantile estimators.

Multiple Myeloma with Myelomatous Pleural Effusion: A Case Report and Review of the Literature

Multiple myeloma (MM) is a malignant neoplasm of plasma cell origin. Pleural effusion may develop in the setting of MM due to various reasons, but myelomatous pleural effusion (MPE) is rare. We report a case of MPE in a patient with advanced MM. A 76-year-old woman with MM was admitted to hospital because of dyspnea. Chest X-ray showed right-sided pleural effusion. Protein electrophoresis of the pleural fluid showed monoclonal protein, and cytology demonstrated monoclonal plasma cells. Hospice care was implemented, and the patient died one month later. We present an analysis of the clinical characteristics of 57 MPE cases reported in the English literature. Our review revealed that MPE patients had poor overall survival irrespective of whether MPE develops in the course of their disease or presents as the initial manifestation of MM. Based on this analysis, MPE is a poor prognostic factor, and aggressive treatment should be considered, especially for patients with early-onset MPE.

Slope of Emphysema Index: An Objective Descriptor of Regional Heterogeneity of Emphysema and an Independent Determinant of Pulmonary Function

OBJECTIVE The purpose of this study was to compare quantitative and visual assessments of regional heterogeneity of emphysema and to investigate the influence of regional heterogeneity on pulmonary function in smoking-related emphysema. MATERIALS AND METHODS We developed an automatic computerized algorithm to quantitatively assess heterogeneity in the upper-lower, anterior-posterior, and central-peripheral directions. The emphysema index was plotted with a linear function (emphysema index slopes: slope of emphysema index in upper-lower direction, slope of emphysema index in anterior-posterior direction, and slope of emphysema index in central-peripheral direction) for consecutive 1-pixel-thick slices using volumetric CT data of 59 patients (58 men and one woman; mean age, 65.7 years). Emphysema index was defined as the percentage area of lung with attenuation values below -950 HU. Visual assessment was performed using a 5-point scoring system. Quantitative and visual assessments were compared. Multiple linear regression was performed to evaluate the influence of emphysema index and emphysema index slopes on the pulmonary function test. RESULTS Quantitative and visual assessments were significantly correlated in both upper-lower (r(2) = 0.40 and r(2) = 0.67 for observers 1 and 2, respectively) and central-peripheral (r(2) = 0.51 and r(2) = 0.47, respectively) directions. Multiple linear regression revealed that emphysema index, slope of emphysema index in upper-lower direction, and slope of emphysema index in anterior-posterior direction were independent determinants of forced expiratory volume in 1 second (FEV(1)) (r(2) = 0.30; p < 0.001). Emphysema index and slope of emphysema index in upper-lower direction were independent determinants of the ratio of FEV(1) to forced vital capacity (FEV(1)/FVC) (r(2) = 0.32; p < 0.001). In addition to higher emphysema index, lower and posterior lung dominance was associated with a decrease in FEV(1) and FEV(1)/FVC. CONCLUSION Computerized, quantitative assessment using the emphysema index slope is comparable to visual assessment in the evaluation of regional heterogeneity of emphysema. In addition to the emphysema index, regional heterogeneity of smoking-related emphysema contributes to impairment of pulmonary function.