Comparison of effects of treatment of primary nocturnal enuresis with oxybutynin plus desmopressin, desmopressin alone or imipramine alone: a randomized controlled clinical trial

PURPOSE: We prospectively evaluated the efficacy of a combination of desmopressin and oxybutynin for treating children with nocturnal enuresis, compared to the single drugs imipramine and desmopressin. MATERIALS AND METHODS: We enrolled 158 patients from 2003 to 2004. Children were randomly assigned to 1 of 3 groups and treated with desmopressin, imipramine or a combination of desmopressin plus oxybutynin. Of these patients 145 (100 boys and 45 girls, mean age 7.8 +/- 2.5 years, range 5 to 15) were followed for more than 6 months. Efficacy was measured at 1, 3 and 6 months in terms of average enuretic frequency, 5-scale response based on change in nocturnal enuretic frequency after treatment and posttreatment enuretic frequency as a percentage of pretreatment baseline frequency. The latter efficacy was classified according to daytime voiding symptoms. Statistical evaluation was performed using chi-square tests and ANOVA. RESULTS: Of the 145 children followed 48 received combination therapy, 49 received desmopressin and 48 received imipramine. A total of 68 patients (47%) had monosymptomatic enuresis and 77 (53%) had polysymptomatic enuresis. Combination therapy produced the best and most rapid results regardless of whether the children had monosymptomatic or polysymptomatic enuresis. CONCLUSIONS: Combination therapy with desmopressin plus oxybutynin for the treatment of pediatric nocturnal enuresis was well tolerated, and gave significantly faster and more cost-effective results than single drug therapy using either desmopressin or imipramine.     

Usefulness of Combined Metabolic–Volumetric Indices of 18F-FDG PET/CT for the Early Prediction of Neoadjuvant Chemotherapy Outcomes in Breast Cancer

Purpose

The purpose of this study was to investigate the usefulness of metabolic-volumetric indices of ¹⁸F- fluorodeoxy-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) for the evaluation of neoadjuvant chemotherapy outcomes in breast cancer.

Methods

Twenty-four patients with locally advanced breast cancer were enrolled in the study. They underwent baseline ¹⁸F-FDG PET/CT scan and received four or six cycles of neoadjuvant chemotherapy, interim ¹⁸F-FDG PET/CT was done after second cycle of chemotherapy. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesions were calculated. Reduction rates of these parameters were obtained between baseline and interim ¹⁸F-FDG PET/CT. Chemotherapy outcomes were assessed using tumor size reduction rate and histological grading system (Miller and Payne system). Reduction rates of SUVmax, MTV, and TLG correlated with chemotherapy outcomes.

Results

MTV and TLG reduction rates showed significant correlation with tumor size reduction rate (R = 0.68, P = 0.0004; R = 0.62, P = 0.002, respectively). However, SUVmax reduction rate showed no significant correlation. MTV and TLG reduction rates were significantly higher in responders than nonresponders, as determined by Miller and Payne system (P < 0.0007, P < 0.002). However, SUVmax reduction rate showed no significant difference. On ROC analysis, the area under the MTV and TLG curves was 0.886, and that of SUVmax was 0.743. Sensitivity, specificity, positive predictive value, and negative predictive value to predict histopathologic response were the same for MTV and TLG, and the values were 100 %, 85.7 %, 83.3 %, and 100 %, respectively (at the reduction rate of 93.2 % for MTV, and 95.8 % for TLG).

Conclusion

Changes of metabolic–volumetric indices successfully reflected the neoadjuvant chemotherapy outcomes. MTV and TLG could be robust indices in discriminating pathologic responder as SUVmax, after neoadjuvant chemotherapy.     

Combined RNA interference of adenine nucleotide translocase-2 and ganciclovir therapy in hepatocellular carcinoma

PurposeThe purpose of this study was to investigate the anticancer effects of combined RNA interference (RNAi) of the adenine nucleotide translocase-2 (ANT2) gene and ganciclovir (GCV) therapy for treatment of hepatocellular carcinoma cells (Huh 7) in an animal model.MethodsThe Huh 7/NTG stable cell line was established by transfection of a vector with the human sodium iodide symporter (hNIS), HSV1-sr39 thymidine kinase (tk), and enhanced green florescent protein (EGFP) fusion gene into Huh 7 cells. mRNA expressions of these genes were evaluated by RT-PCR analysis. The functions of hNIS and HSV1-sr39tk were verified with ¹²⁵I uptake and ³H-penciclovir (PCV) uptake tests. EGFP and hNIS expression was confirmed with confocal microscopy after immunocytochemical staining. We treated the tumor cells with ANT2 shRNA or GCV or both ANT2 shRNA and GCV and treated the in vivo mouse model with a Huh 7/NTG tumor xenograft. The therapeutic effects of the in vivo study were assessed with caliper measurements and gamma camera imaging using ^99mTc-pertechnetate.ResultsHuh 7/NTG cells showed a cell number-dependent increase in ¹²⁵I uptake and a 24-fold higher ³H-PCV uptake compared to parent Huh 7 cells. Huh 7/NTG cells transfected with ANT2 shRNA had lower ANT2 mRNA expression and more impaired proliferation activity than cells transfected with scramble shRNA. Proliferation of Huh 7/NTG cells was also inhibited by GCV treatment. Combined GCV and ANT2 shRNA therapy further inhibited cell proliferation in the in vitro study. The combined therapy with GCV and ANT2 shRNA showed a further decrease in tumor growth in the mouse model.ConclusionsOur results suggest that the combined RNA interference with ANT2 and GCV therapy inhibited hepatocellular carcinoma cell proliferation more than single GCV therapy or ANT2 shRNA therapy in vitro and in vivo. Therefore it could be applied treating incurable hepatocellular carcinoma.     

Staging of Hepatic Fibrosis: Comparison of Magnetic Resonance Elastography and Shear Wave Elastography in the Same Individuals

Objective

To cross-validate liver stiffness (LS) measured on shear wave elastography (SWE) and on magnetic resonance elastography (MRE) in the same individuals.

Materials and Methods

We included 94 liver transplantation (LT) recipients and 114 liver donors who underwent either MRE or SWE before surgery or biopsy. We determined the technical success rates and the incidence of unreliable LS measurements (LSM) of SWE and MRE. Among the 69 patients who underwent both MRE and SWE, the median and coefficient of variation (CV) of the LSM from each examination were compared and correlated. Areas under the receiver operating characteristic curve in both examinations were calculated in order to exclude the presence of hepatic fibrosis (HF).

Results

The technical success rates of MRE and SWE were 96.4% and 92.2%, respectively (p = 0.17), and all of the technical failures occurred in LT recipients. SWE showed 13.1% unreliable LSM, whereas MRE showed no such case (p < 0.05). There was moderate correlation in the LSM in both examinations (r = 0.67). SWE showed a significantly larger median LSM and CV than MRE. Both examinations showed similar diagnostic performance for excluding HF (Az; 0.989, 1.000, respectively).

Conclusion

MRE and SWE show moderate correlation in their LSMs, although SWE shows higher incidence of unreliable LSMs in cirrhotic liver.     

Primary Endobronchial Marginal Zone B-Cell Lymphoma of Bronchus-Associated Lymphoid Tissue: CT Findings in 7 Patients

Objective

To investigate CT and ¹⁸F-flurodeoxyglucose (¹⁸F-FDG) positron-emission tomography/CT findings of primary endobronchial marginal zone B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT).

Materials and Methods

From June 2006 through April 2012, seven patients (six female, one male; age range, 21-61 years; mean age, 49 years) were examined who were pathologically diagnosed with the primary endobronchial marginal zone B-cell lymphoma of BALT. We evaluated the locations and characteristics of the lesions on CT and ¹⁸F-FDG-PET/CT scans. The lesions were classified into the following three patterns: 1) solitary intraluminal nodule; 2) several tiny nodular protrusions; and 3) diffuse wall thickening.

Results

A solitary intraluminal nodule was observed in four patients (57.1%), several tiny nodular protrusion in two patients (28.6%), and diffuse wall thickening in one patient (14.3%). The lesions were categorized into 3 major locations: confined to the trachea (n = 3), confined to the lobar bronchus (n = 2), and diffuse involvement of the trachea and both main bronchi (n = 2). All lesions demonstrated homogeneous iso-attenuation as compared with muscle on pre- and post-enhancement scans. Secondary findings in the lungs (n = 3; 42.9%) included postobstructive lobar atelectasis (n = 1), air trapping (n = 1), and pneumonia (n = 1). On ¹⁸F-FDG-PET/CT (n = 5), 4 lesions showed homogeneous uptake with maximum standardized uptake values (mSUV), ranging 2.3-5.7 (mean mSUV: 3.3). One lesion showed little FDG uptake.

Conclusion

Primary endobronchial marginal zone B-cell lymphoma of the BALT manifests as three distinct patterns on CT, with the solitary intraluminal nodule presenting as the main pattern. Most lesions demonstrate homogeneous but weak FDG uptake on ¹⁸F-FDG-PET/CT.     

Quantitative assessment of shear-wave ultrasound elastography in thyroid nodules: diagnostic performance for predicting malignancy

Objectives

To evaluate the predictability of shear-wave ultrasound elastography (SWE) for thyroid malignancy and to compare the diagnostic performances of SWE and B-mode US.

Methods

Retrospective review of 99 patients who underwent SWE before US-guided fine-needle aspiration of thyroid nodules was performed. SWE elasticity indices of the mean (E_mean ), maximum (E_max), and minimum (E_min) of nodules were measured. Diagnostic performance of SWE was compared with that of B-mode US.

Results

Among a total of 99 nodules, 21 were papillary thyroid carcinoma (PTC) and 78 were benign. E_mean, E_max, and E_min were significantly higher in PTCs than in benign nodules (P?<?0.001). Sensitivity and specificity for predicting malignancy were 76.1 %, 64.1 % with E_max (65 kPa), 61.9 %, 76.1 % with E_min (53 kPa), and 66.6 %, 71.6 % with E_mean (62 kPa). Areas under the ROC curves (Az) of SWE values were not significantly different from those of US categories on B-mode US. However, combining E_mean and E_min with B-mode US of probably benign lesions improved the specificity (P?=?0.02, 0.007) for predicting PTC.

Conclusions

The quantitative parameter of SWE was significantly higher in PTC than in benign nodules, and combined use of quantitative SWE and B-mode US provided higher specificity for predicting malignancy.

Key Points

? Quantitative shear-wave elastography (SWE) helps differentiate benign from malignant nodules ? SWE and conventional ultrasound have comparable diagnostic performance for predicting thyroid malignancy ? Combined quantitative SWE and B-mode ultrasound is highly specific for thyroid malignancy     

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 (FEV(1))/forced vital capacity (FVC) (R = 0.49, P = 0.044), PBV positively correlated with FEV(1)/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 FEV(1) (R = 0.63, P = 0.017) and FEV(1)/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, kappa = 0.47 (P < 0.001); PBV 78.6% (reader 1) and 78.6% (reader 2) of the patients, kappa = 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.     

Texture-based quantification of pulmonary emphysema on high-resolution computed tomography: comparison with density-based quantification and correlation with pulmonary function test

PURPOSE: To develop a system for texture-based quantification of emphysema on high-resolution computed tomography (HRCT) and to compare it with density-based quantification in correlation with pulmonary function test (PFT). MATERIALS AND METHODS: Two hundred sixty-one circular regions of interest (ROI) with 16-pixel diameter [66 ROIs representing typical area of normal lung; 69 representing bronchiolitis obliterans (BO); 64, mild emphysema (ME); and 62, severe emphysema (SE)] were used to train the automated classification system based on the Support Vector Machine classifier and on variable texture and shape features. An automated quantification system was developed with a moving ROI in the lung area, which classified each pixel into 4 categories. To validate the system, the HRCT and standard-kernel-reconstructed volumetric CT data of 39 consecutive patients with emphysema were included. Using this system, the whole lung area was evaluated, and the area fractions of each class were calculated (normal lung%, BO%, ME%, SE%, respectively). The emphysema index (EI) of texture-based quantification was defined as follows: (0.3 x ME% + SE%) (TEI). EIs from density-based quantification with a threshold of -950 Hounsfield Units, were measured on both HRCT (DEI_HR_2D) and on volumetric CT (DEI_standard_3D). The agreement between TEI, DEI_HR_2D, and DEI_standard_3D was assessed using interclass correlation coefficients (ICC). Correlation of the results on the TEI with the PFT results was compared with the results of the DEI_standard_3D and the DEI_HR_2D with Spearman's correlation test. To evaluate the contribution of each texture-based quantification lesion (BO%, ME%, SE%) on PFT, multiple linear regression analysis was performed. RESULTS: The calculated TEI (19.71% +/- 17.98%) was well correlated with the DEI_standard_3D (19.42% +/- 14.30%) (ICC = 0.95), whereas the ICC with DEI_HR_2D (37.22% +/- 9.42%) was 0.43. TEI showed better correlation with PFT than DEI_standard_3D or DEI_HR_2D did [R = 0.71 vs. 0.67 vs. 0.61 for forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC); 0.54 vs. 0.50 vs. 0.43 for diffusing capacity (DLco), respectively]. Multiple linear regression analysis revealed that the BO% and SE% areas were independent determinants of FEV(1)/FVC, whereas the ME% and the SE% were determinants of DLco. CONCLUSION: Texture-based quantification of emphysema using an automated system showed better correlation with the PFT results than density-based quantification. Separate quantification of the BO, ME, and SE areas showed a different contribution of each component to the FEV(1)/FVC and the DLco. The proposed system can be successfully used for detailed regional and global evaluation of lung lesions on HRCT scanning for emphysema.     

Effects of anesthetic agents on cellular <Superscript>123</Superscript>I-MIBG transport and in vivo <Superscript>123</Superscript>I-MIBG biodistribution

Objectives Small animal imaging with meta-iodobenzylguanidine (MIBG) allows characterization of animal models, optimization of tumor treatment strategies, and monitoring of gene expression. Anesthetic agents, however, can affect norepinephrine (NE) transport and systemic sympathetic activity. We thus elucidated the effects of anesthetic agents on MIBG transport and biodistribution. Methods SK-N-SH neuroblastoma and PC-12 pheochromocytoma cells were measured for ¹²³I-MIBG uptake after treatment with ketamine (Ke), xylazine (Xy), Ke/Xy, or pentobarbital (Pb). NE transporters were assessed by Western blots. Normal ICR mice and PC-12 tumor-bearing mice were injected with ¹²³I-MIBG 10 min after anesthesia with Ke/Xy, Ke, Xy, or Pb. Plasma NE levels and MIBG biodistribution were assessed. Results Cellular ¹²³I-MIBG uptake was dose-dependently inhibited by Ke and Xy but not by Pb. Treatment for 2 h with 300 μM Ke, Xy, and Ke/Xy decreased uptake to 46.0 ± 1.6, 24.8 ± 1.5, and 18.3 ± 1.6% of controls. This effect was completely reversed by fresh media, and there was no change in NE transporter levels. In contrast, mice anesthetized with Ke/Xy showed no decrease of MIBG uptake in target organs. Instead, uptakes and organ-to-blood ratios were increased in the heart, lung, liver, and adrenals. Plasma NE was notably reduced in the animals with corresponding decreases in blood MIBG, which partly contributed to the increase in target organ uptake. Conclusion In spite of their inhibitory effect at the transporter level, Ke/Xy anesthesia is a satisfactory method for MIBG imaging that allows favorable target tissue uptake and contrast by reducing circulating NE and MIBG. Bong-Ho Ko and Jin-Young Paik equally contributed to this work. This work was supported by the Korea Research Foundation Grant KRF-2005-202-E00116. Presented in part at the fifth Annual Meeting of the Society for Molecular Imaging, Hawaii, August 30–September 2, 2006.     

The kinematics of fixed- and mobile-bearing total knee arthroplasty

The success of any total knee arthroplasty (TKA) is influenced by a complex interaction between component geometry and the surrounding soft tissues. The objective of this study was to investigate posterior femoral translation and tibial rotation in a single design posterior-stabilized TKA offering fixed- and mobile-bearing tibial components. Specifically, we examined whether mobile-bearing TKA restores normal knee translation and rotation better than fixed-bearing TKA design. Eleven human knee specimens retrieved postmortem were tested using a robotic system. The translation and rotation of the intact and reconstructed knees were compared. The data indicate that for all knees, posterior femoral translation occurs along the passive path and under muscle loading conditions. Furthermore, increasing flexion angle corresponded with increased internal tibial rotation. Femoral translation and tibial rotation for fixed- and mobile-bearing posterior-stabilized TKAs were similar despite component design variations. However, both arthroplasties only partially restored intact knee translation and rotation. The data presented here may serve as an aid in the development of a rationale for additional improvement in surgical techniques and prosthesis design, so that normal knee function may be restored.