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A physiologically-based pharmacokinetic (PBPK) model was developed for YH4808, a novel potassium-competitive acid blocker, using the SimCYP® Simulator based on the physicochemical, in vitro preclinical and clinical data of YH4808. The PBPK model was optimized using YH4808 concentrations obtained from the single-dose phase I clinical trial. Overall, the PBPK model adequately predicted the observed pharmacokinetic profiles of YH4808 in humans. The pharmacokinetic profiles of YH4808 after multiple oral administrations were predicted using a refined PBPK model. The ratios of model-predicted to observed Cmax, AUCinf and AUCτ values on Day 1 and Day 7 at 100 mg were 0.7–1.0. However, the model failed to predict a decreased exposure after multiple oral administration particularly at higher doses of 200 and 400 mg. The reduced solubility of YH4808 at higher pH was hypothesized as the main cause of the reduction in exposure such that absorption was decreased as pH was increased. This hypothesis was confirmed by PBPK modeling and simulation, where intragastric pH was increased by YH4808.

Clostridioides difficile toxins TcdA and TcdB are large clostridial glucosyltransferases which are the main pathogenicity factors in C. difficile-associated diseases. Four highly conserved cysteines are present in all large clostridial glucosyltransferases. In this study we focused on the conserved cysteine 2232 within the combined repetitive oligopeptide domain of TcdB from reference strain VPI10463 (clade I). Cysteine 2232 is not present in TcdB from hypervirulent strain R20291 (clade II), where a tyrosine is found instead. Replacement of cysteine 2232 by tyrosine in TcdBV PI10463 reduced binding to the soluble fragments of the two known TcdB receptors, frizzled-2 (FZD2) and poliovirus receptor-like protein-3/nectin-3 (PVRL3). In line with this, TcdBR20291 showed weak binding to PVRL3 in pull-down assays which was increased when tyrosine 2232 was exchanged for cysteine. Surprisingly, we did not observe binding of TcdBR20291 to FZD2, indicating that this receptor is less important for this toxinotype. Competition assay with the receptor binding fragments (aa 1101–1836) of TcdBV PI10463 and TcdBR20291, as well as antibodies newly developed by antibody phage display, revealed different characteristics of the yet poorly described delivery domain of TcdB harboring the second receptor binding region. In summary, we found that conserved Cys-2232 in TcdB indirectly contributes to toxin–receptor interaction.

Objective: Fine-needle aspiration cytology (FNAC) based on a liquid-based preparation is a safe and valuable diagnostic tool. However, due to unfamiliarity with this method and the considerably altered morphology that is associated with it, diagnosing renal cell carcinoma (RCC) from this type of preparation remains a challenge for cytopathologists. The aim of this study was to evaluate the cytomorphological characteristics of SurePath™ (SP)-based preparations compared with conventional smear (CS), and also the role of SP-based FNAC in the diagnosis of clear-cell RCC (CRCC), the most common primary renal malignancy. Study Design: Ex vivo FNAC of both tumors and normal renal parenchyma was prepared from 73 cases. Comparative cytomorphological analysis between liquid-based cytology (LBC) and CS as well as Fuhrman nuclear grading (FNG) was carried out. Immunocytochemistry was performed from normal and CRCC cytology specimens. Results: Normal renal cytology (NRC) showed no significant morphological differences between LBC and CS. For CRCC, LBC showed small, fragmented cell clusters, a 3-dimensional configuration, distinct cytoplasmic vacuoles, and irregular nuclear contours when compared with CS. FNG was overgraded with LBC compared to with CS. AMACR was the most valuable immunocytochemical marker for distinguishing CRCC from NRC. Conclusion: Once cytopathologists become familiar with the altered cytomorphological features of CRCC, FNAC, along with immunocytochemistry, may prove helpful for diagnosis.

Background We subjected chemokine (C-X-C motif) ligand 12 (CXCL12) to immunohistochemistry to determine its utility as a novel diagnostic marker for papillary thyroid carcinoma (PTC) in comparison to cytokeratin 19 (CK19), Hector Battifora mesothelial epitope-1 (HBME-1), and galectin-3. Methods We analyzed the expressions of CXCL12, CK19, HBME-1, and galectin-3 using immunohistochemical staining in 258 cases of thyroid lesions (196 PTCs and 62 thyroid lesions excluding PTC). Results Remarkably, CXCL12 expression was exclusively found in PTC compared to other thyroid lesions (90.8% vs 3.2%; p < .001). In total, 91.1% (62 of 68) of the variant PTCs and 90.6% of conventional type (116 of 128) were associated with CXCL12 immunohistochemical expression, irrespective of the histological subtype. In contrast, very few of the thyroid lesions, excluding PTC, were positive for CXCL12 (2 of 62; 3.2%). Diagnostic performances for PTCs were as follows: sensitivity, 90.8%; specificity, 96.8%; positive predictive value, 98.9%; negative predictive value, 76.9%; and diagnostic accuracy, 92.2%. Conclusion Our findings indicate that CXCL12 might serve as an effective novel supplementary diagnostic marker for PTC. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1005–1012, 2014

To determine the optimal surface-rendering threshold value for three-dimensional (3D) endoluminal computed tomographic (CT) colonographic images for accurate manual polyp measurement, with direct measurement of simulated polyps as the reference standard, and to assess the agreement between manual 3D measurements and automated measurements.Institutional review board approval was not required for the experimental study with pig colons obtained at an abattoir but was obtained for the use of patient data, with waiver of informed consent. Eighty-six simulated polyps (reference size, 3-15 mm) and 14 human polyps (approximate size, 5-20 mm) were included. Automated polyp measurements and manual measurements with endoluminal views that were surface rendered at threshold values of -800, -700, -600, and -500 HU were performed by one observer. Agreement between CT colonographic measurements and reference sizes and between manual and automated measurements were assessed by using the Bland-Altman method.For simulated polyps, mean measurement difference between the observed size and reference size was 0.86 mm (95% limits of agreement: -0.52 mm, 2.24 mm), 0.55 mm (95% limits of agreement: -0.75 mm, 1.85 mm), 0.20 mm (95% limits of agreement: -1.11 mm, 1.50 mm), and -0.08 mm (95% limits of agreement: -1.43 mm, 1.27 mm) for -800, -700, -600, and -500 HU, respectively. Mean measurement difference was 0.09 mm (95% limits of agreement: -1.49 mm, 1.67 mm) for automated measurement. Manual polyp size at -500 HU (P = .277) and automated polyp size (P = .288) were not significantly different from reference size. For human polyps, 10 polyps, excluding four lesions that were large, lobulated, or located adjacent to an edge of the haustral fold, showed accurate automated demarcation of lesion boundaries. Automated measurements of the 10 polyps showed the closest agreement with manual measurements at -500 HU.The optimal surface-rendering threshold value for accurate polyp measurement is approximately -500 HU. Automated measurements agree closely with manual measurements at the optimal threshold value for well-circumscribed smooth rounded polyps.

Primary liposarcoma of the liver is extremely rare. We report here on a case of primary well-differentiated liposarcoma in the left hepatic lobe of a 63-year-old woman. Abdominal ultrasonography showed a well-defined, echogenic, round mass. Abdominal computed tomography (CT) and magnetic resonance (MR) images showed an almost fatty, lobulated mass with a few, random distributed vascular structures and a small area of nodular enhancement. The resected tumor appeared as a well-defined, round, tan-yellow mass. Histological analysis showed a well-differentiated liposarcoma.

The aim of this study is to evaluate the biological role and clinical implications of silent mating type information regulation 2 homolog 1 (SIRT1) as a novel candidate for target therapy in triple negative breast cancer (TNBC) for which there is no specific agent. 344 patients who received surgical resection for TNBC from January 2003 to December 2006 at Seoul National University Hospital were enrolled, and the role of SIRT1 protein was evaluated via immunohistochemistry on tissue samples. In vivo experiments to evaluate tumor invasiveness were carried out with three human TNBC cell lines following SIRT1-siRNA transfection. Expression of SIRT1 significantly correlated with lymph node metastasis (p = 0.008). In multivariate analysis, SIRT1 expression (p = 0.011), T stage (p = 0.014), and lymphatic invasion (p

To compare prospectively obtained static two-dimensional (2D) and three-dimensional (3D) ultrasonographic (US) images in the diagnostic performance of radiologists with respect to the differentiation of benign from malignant solid breast masses with histopathologic examination as the reference standard.This study had institutional review board approval, and patient informed consent was obtained. Conventional 2D and 3D US images were obtained from 141 patients (age range, 25-71 years; mean age, 46 years) with 150 solid breast masses (60 cancers and 90 benign lesions) before excisonal or needle biopsy. Four radiologists who had not performed the examinations independently reviewed 2D US images and stored 3D US data and provided a level of suspicion concerning probability of malignancy. The sensitivity, specificity, and negative predictive values of 2D images were compared with those of 3D US images.For all readers, 3D US images were the same as or better than 2D US images in terms of sensitivity (100% vs 100% for reader 1; 100% vs 98% for reader 2; 98% vs 93% for reader 3; 93% vs 92% for reader 4), specificity (58% vs 56% for reader 1; 51% vs 46% for reader 2; 83% vs 72% for reader 3; 86% vs 84% for reader 4), and negative predictive values (100% vs 100% for reader 1; 100% vs 98% for reader 2; 99% vs 94% for reader 3; 95% vs 94% for reader 4). These differences, however, were not statistically significant (P.05).The performance of the radiologists with respect to the characterization of solid breast masses with static 2D US images was similar to that with 3D US data.

Toluene is widely used in adhesive, printing, painting and petroleum industries in many countries. This study was conducted to examine the effect of chronic exposure to toluene below 100 ppm on neurobehavioral performance using a computerized neurobehavioral test battery that emphasizes simple instructions and practice prior to testing. The Behavioral Assessment and Research System (BARS) with Korean language instructions was administered to 54 workers from three different industries: oil refinery, gravure printing, and rubber boat manufacturing. The battery consisted of the following tests: Digit Span (DS), Simple Reaction Time (SRT), Selective Attention (SAT), Finger Tapping (FT), and Symbol Digit (SD). Urine was collected at the end-of-shift to analyze urinary hippuric acid to assess exposure level to toluene. Based on the previous air toluene level, workers were divided into three groups: Low (21 workers, less than 10 ppm), Moderate (13 workers, 20–30 ppm) and High (20 workers, 70–80 ppm) exposure status. Analysis of Covariance (ANCOVA) adjusting for age, education and work duration as covariates, was performed to examine the relationship between the neurobehavioral performance and the exposure groups. Poorer performance of the High exposure group was found on FT-preferred ( F = 7.034, p = 0.002) and SAT latency ( F = 11.710, p = 0.000). Age showed a significant correlation with SD ( r = 0.417, p = 0.002) and SAT number correct ( r = −0.460, p = 0.000). Years of education and work duration were not significantly correlated with any items. This study supports that toluene exposure below 100 ppm is associated with neurobehavioral changes and that high-level toluene exposure could cause not only attention and concentration, but also motor performance deficits.

Purposes Lung squamous cell carcinoma (SQCC) is the second-largest histological subtype of non-small cell lung cancer, but relatively few biomarkers are available compared to adenocarcinoma. Recently, chemokines and their receptors have been suggested to play important roles in the initiation or progression of cancers. In this study we examined the expression of chemokines and their receptors in human lung SQCC. Methods For mRNA expression of chemokines their receptors study, tumors and their matched normal lung specimens were collected from fresh frozen samples of 10 patients. For immunohistochemistry (IHC) study, formalin-fixed paraffine-embedded samples of 35 patients with primary lung SQCC were collected. All samples were from patients who were subjected to curative surgical resection at Dongnam Institute of Radiological and Medical Sciences. The mRNA was extracted by Quiagen RNeasy kit and the human RT2ProfilerPCR arrays for Chemokines/Receptors (SA Biosciences) was employed to determine the mRNA expression. Also, IHC was used to demonstrate their protein expression. Results The expression profiles of 84 chemokines and their related genes were compared across the tumors and their matched normal lung tissues. Among them, mRNA expression levels of CXCL14 (p=0.000) and CXCR7 (p=0.025) were significantly upregulated in tumor. CXCL14 and CXCR7 protein expression by IHC were detected in 25 (71%, p=0.000) and 21 (60%, p=0.000) of 35 cases for tumor, respectively. However, normal lung tissues showed no protein expression for CXCL14 and CXCR7. We also analyzed the correlation between clinicopathologic features (age, stage, tumor size, lymph node involvement, lymphovascular and perineural invasion and differentiation of tumor) and protein expression of CXCL14 and CXCR7. Although not significant, CXCL14 protein expression was more detected in the advanced stage (stage I/II, 60% vs III/IV, 90%) (p=0.120), lymphatic invasion (Yes, 82% vs No, 41%) (p=0.146) and perineural invasion (Yes, 100% vs No, 57%) (p=0.067). CXCR7 protein expression was significantly higher in advanced stage (stage I/II, 11/24, 46% vs III/IV, 10/10, 100%) (p=0.005) and lymphatic invasion (Yes, 13/16, 81% vs No, 8/18, 44%) (p=0.039). Conclusions This study demonstrated that mRNA expression level of CXCL14 and CXCR7 were significantly higher in SQCC compared to those in normal tissue. CXCR7 protein expression was detected significantly higher in advanced stage and lymphatic invasion. Our results indicated that CXCL14 and CXCR7 might play important roles in carcinogenesis and further study to elucidate their role in SQCC is required. Citation Format: YoonHee Choi, Soo Young Chung, Yoo Sang Yoon, Jae Hyun Kim, Ha-young Lee, Kyung A Kwon, Bong-Gun Seo, Hee Sam Na, Sung Sook Lee. CXCL14 and CXCR7 expression are upregulated in human squamous lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4664. doi:10.1158/1538-7445.AM2017-4664

Chromatin remodeling mediated by histone acetylation might be involved in the pathophysiology and the treatment of depression. Recently, it has been reported that the histone deacetylase (HDAC) inhibitors, such as sodium butyrate (SB), could be a potential therapeutic agent for depression treatment. In the present study, we aimed to clarify the antidepressant mechanism of SB in the hippocampus. The mice were exposed to chronic restraint stress (CRS) for 14 consecutive days (2 h/day) to induce depression-like behaviors. To assess depression-like behaviors, sucrose preference test, light dark test (LD), tail suspension test (TST), and forced swim test (FST) were performed after CRS. We observed that CRS decreased HDAC2 and 5 mRNA and protein levels in the hippocampus. In addition, SB co-treatment decreased the depression-like behaviors that are induced by CRS. SB prevented and normalized the phosphorylation of cAMP response element binding protein (pCREB), acetylation of histone H3 (AceH3), HDAC2, and brain-derived neurotrophic factor (BDNF) expression level that were decreased by CRS in the hippocampus. These results suggest that the decreased HDAC2 and 5 expressions in the hippocampus of CRS may be a type of spontaneous coping response against CRS. However, it seems to be unsuccessful to prevent depression induction since reduction of pCREB, AceH3 and BDNF were accompanied by CRS in the hippocampus. Moreover, the reduced AceH3 level may be associated with the decreased pCREB, which appears to lead to the decreased BDNF.

We subjected chemokine (C-X-C motif) ligand 12 (CXCL12) to immunohistochemistry to determine its utility as a novel diagnostic marker for papillary thyroid carcinoma (PTC) in comparison to cytokeratin 19 (CK19), Hector Battifora mesothelial epitope-1 (HBME-1), and galectin-3.We analyzed the expressions of CXCL12, CK19, HBME-1, and galectin-3 using immunohistochemical staining in 258 cases of thyroid lesions (196 PTCs and 62 thyroid lesions excluding PTC).Remarkably, CXCL12 expression was exclusively found in PTC compared to other thyroid lesions (90.8% vs 3.2%; p.001). In total, 91.1% (62 of 68) of the variant PTCs and 90.6% of conventional type (116 of 128) were associated with CXCL12 immunohistochemical expression, irrespective of the histological subtype. In contrast, very few of the thyroid lesions, excluding PTC, were positive for CXCL12 (2 of 62; 3.2%). Diagnostic performances for PTCs were as follows: sensitivity, 90.8%; specificity, 96.8%; positive predictive value, 98.9%; negative predictive value, 76.9%; and diagnostic accuracy, 92.2%.Our findings indicate that CXCL12 might serve as an effective novel supplementary diagnostic marker for PTC.

Enterovirus 70 (EV70) is the causative agent of acute hemorrhagic conjunctivitis (AHC), for which no effective vaccine is available. This study revealed a high reactivity of the N-terminal region of EV70 VP1 (VP1-1) with an anti-EV70 mouse serum. The analysis of overlapping synthetic peptides of VP1-1 identified a B-cell epitope in this region. The E-peptide (14-ANTVESEIKAELGVI-28) showing the highest reactivity with the anti-EV70 serum induced neutralizing antibodies in mice and reduced the virus titer in the eyes, suggesting that it is a candidate vaccine against AHC caused by EV70.

Objective: Preoperative fine needle aspiration biopsy (FNAB) has become the initial diagnostic method for papillary thyroid carcinoma (PTC). Identification of cytomorphologic factors predicting lymph node metastasis (LNM) is clinically important for determining the appropriate treatment regimen due to the high rate of lymph node involvement in PTC at the time of diagnosis. Hobnail features (HF) have previously been described as potential histomorphologic features in the histological examination of PTC. This study evaluated the value of HF as a predictor of LNM. Study Design: Histologically confirmed FNABs (n = 111) of papillary thyroid microcarcinoma prepared by the liquid-based method were enrolled. Along with other cytomorphologic parameters, HF were evaluated for their value in predicting LNM. Results: Although HF were closely correlated with cytoplasmic vacuoles of tumor cells and background macrophages (p < 0.05), which were considered diagnostic indicators of PTC with cystic changes, HF were only found to be significantly correlated with LNM (p = 0.008). The BRAFV660E mutation was not associated with LNM. All combinations including HF were revealed as stronger predictors of LNM (odds ratios: 2.254-2.524, p < 0.05). Conclusions: HF, a distinctive cytomorphologic feature, may be used as a factor predicting LNM in preoperative FNAB of PTC.

Objective Cervical tuberculous lymphadenitis (CTBL) is still an important cause of neck mass in many countries. The purpose of this study is to analyze the CT findings of CTBL and compare them with those of malignant lymphadenopathies and pyogenic abscesses in the neck. Materials and methods We retrospectively reviewed the CT scans of 32 CTBLs, 25 malignant lymphadenopathies, and 12 pyogenic abscesses in the neck. Attenuation value, enhancement pattern, and surrounding fat plane were evaluated. Results The CT findings of CTBL were classified into four types: type 1, homogeneous soft tissue density; type 2, central low density and peripheral rim enhancement with relative preservation of surrounding fat planes; type 3, multilocular central low densities and peripheral rim enhancement with obliteration of surrounding fat planes; and type 4, large confluent low density with peripheral rim enhancement and loss of lymph node architecture. Among the 32 cases of CTBL, type 3 was most frequently noted (59.4%) followed by type 2 (21.9%), type 4 (15.6%), and type 1 (12.5%). The enhancing rim of CTBL was usually thick and irregular in contrast to some malignant lymph nodes showing thin and regular rim enhancement. The degree of surrounding fat plane obliteration was less in type 4 CTBL than in pyogenic cervical abscess. Conclusion Cervical tuberculous lymphadenitis usually shows a central low density and peripheral rim enhancement that tends to be thick and irregular compared with a malignant lymphadenopathy. Multilocular low densities with peripheral enhancement and a large confluent low density with less degree of fat plane obliteration than a pyogenic abscess are suggestive features of advanced CTBL.

It has been reported that hypobaric hypoxia exposure by high altitude is responsible for neuropsychological impairment. In the present study, we examined an effect of hypobaric hypoxia on the writhing test. The ICR mice were exposed in hypobaric chamber with several altitudes (5000, 10,000 or 20,000 ft) for 1 or 2 h, and then immediately injected intraperitoneally (i.p.) with 1% acetic acid for writhing test. Our results show that both 10,000 ft and 20,000 ft exposure induce antinociceptive effect in writhing test, but 5,000 ft does not. In addition, this antinociceptive effect was abolished by L-NAME (nitric oxide synthase inhibitor) pre-treated intraperitoneally, but not naloxone (non-specific opioid receptor antagonist). Furthermore, we examined that neuronal NOS immunoreactivities in the hypothalamus (paraventricular nucleus and arcuate nucleus) were increased by hypobaric hypoxic exposure (10,000ft). These results suggest that hypobaric hypoxic-induced antinociception may be associated with neuronal NOS IR in the hypothalamus.

e22099 Background: Lung squamous cell carcinoma (SQCC) is the second-largest histological subtype of non-small-cell lung cancer, but relatively less biomarkers are available compared to adenocarcin...

To assess the frequency and degree of air trapping at thin-section computed tomography (CT) of the lung in relation to age and smoking history in asymptomatic subjects.Thin-section CT of the lung was performed prospectively at end inspiration and end expiration in 82 subjects (27 smokers, 55 nonsmokers) without any history of pulmonary diseases and without present pulmonary symptoms. The frequency and degree of air trapping were evaluated according to age and smoking status.The overall frequency of air trapping was 52% (43 of 82 subjects, kappa = 0.72). Air trapping was found in three of 13 (23%), seven of 17 (41%), nine of 18 (50%), 11 of 17 (65%), and 13 of 17 (76%) subjects aged 21-30, 31-40, 41-50, 51-60, and greater than or equal to 61 years, respectively. The frequency of air trapping increased with age (P.05). The degree of air trapping had a significant correlation with age (r = 0.523, P.001) and was higher in smokers with a smoking history of more than 10 pack-years (P.05).Air trapping was found in approximately 50% of asymptomatic subjects. The frequency of air trapping increased with age, and its severity increased with age and smoking.

Purpose : Our goal was to evaluate CT findings of tuberculous abscess in the retromammary region of the breast. Method : Four patients with tuberculosis extending from the retromammary region to the pleura were examined by CT and the findings were evaluated. All cases were also examined with mammography and two cases were evaluated with sonography. Diagnosis was confirmed by acid-fast bacillus stain, culture, and histologic examination. Results : Mammography showed relatively smoothly marginated, round mass density in two cases, nodular density in one, and focal bulging of the pectoral wall in one. A sonogram demonstrated in two cases a fistulous connection from the heterogeneous, fluid-containing lesion with floating internal debris in the retromammary region to the thoracic cavity. In all four cases, CT showed relatively smoothly marginated, inhomogeneous, hypodense lesions with surrounding rims of the cold abscess type. A direct fistulous connection from the retromammary lesion through the thoracic wall into the pleura was seen in two cases. Destroyed rib fragments within the abscess were noted in two cases. Conclusion : A tuberculous abscess in the retromammary region usually showed on CT a focal, smoothly marginated, inhomogeneous, hypodense lesion with a surrounding enhancing rim. A direct fistulous connection with the pleura or a destroyed rib fragment in the abscess as revealed by CT can be helpful in the differential diagnosis of other infectious types of retromammary abscess.

To compare the specific information provided by ultrasound (US) and galactography and to appreciate the clinical applicability of US as a primary diagnostic method for breast tumors associated with nipple discharge, a comparative study of each method in 15 patients with ductal tumors of the breast was performed. To evaluate the smallest anatomical unit of the lactiferous system demonstrable by US, 30 patients with normal lactating breasts were examined prospectively. The smallest anatomical ductal unit that could be evaluated with US in the normal lactating breast was the terminal duct lobular unit (TDLU). US is superior to galactography in detecting masses smaller than 0.5 cm or lesions involving multiple ducts. Galactography is better for visualizing the duct system and detecting calcification. In conclusion, US serves as a primary noninvasive diagnostic tool in patients with clinically suspicious breast tumor associated with bloody nipple discharge, but galactography also should be done in specific circumstances.

Bee sting therapy is a folk remedy used for arthralgia. An adverse reaction to bee sting therapy can be variable, ranging from a local inflammatory reaction to generalized anaphylaxis. There have been reports of dermatologic findings pertaining to bee sting granulomas, which results from a foreign body reaction to the persistence of venom and stinger at the sting site. However to the best of our knowledge, the radiologic findings of bee sting granulomas have not been reported on in Korea. We describe the ultrasound and MRI findings of bee sting granulomas at the lower extremity in a 36-year-old woman who underwent bee-sting therapy for osteoarthritis of the knee joints 3 months prior.

Recognition that many patients with benign sclerosing mediastinitis have smoldering disease responsible for failure of surgical procedures or for development of collateral circulation in patients with superior vena caval obstruction has markedly improved management of these difficult patients. Histoplasmosis complement fixation titers have been used to detect unsuspected subacute disease and to follow the therapeutic adjunctive management with ketoconazole, an oral antifungal agent. Twenty-two patients with benign sclerosing mediastinitis demonstrated a variety of symptoms relating to the area of compression: superior vena cava, 13; esophagus, 3; pulmonary artery and pericardium, 3; and trachea, 3. Histoplasmosis was documented in 12 patients. Operation is used initially for diagnosis, to rule out carcinoma, and to treat the complications: superior vena caval reconstruction, 6; tracheal decompression, 2; right middle lobectomy, 1; esophageal decompression, 2; division of tracheoesophageal fistula, 1; and release of pericardial effusion and cardiac tamponade, 1. Postcardiotomy syndrome occurred in 1 patient and wound infection in another. No deaths resulted. In 6 cases of histoplasmosis, symptoms recurred in 100% of patients and were successfully managed with ketoconazole treatment, and then clinical progress was monitored with serial histoplasmosis complement fixation studies. One patient had four superior vena caval reconstructions at an outside hospital, each 1 year apart, with symptoms recurring each time. With ketoconazole therapy alone, she has been asymptomatic for more than 2 years. Vigorous search for a fungal cause may even obviate the necessity for surgical intervention. If an operation is necessary, preoperative and postoperative use of ketoconazole has assured success.

Purpose: Malignant phyllodes tumors are rare breast tumors. Information on the prognosis and optimal treatment of these lesions is not yet sufficient. The aim of this study was to determine parameters that predict the recurrence of malignant phyllodes tumors of the breast. Methods: Retrospectively, we reviewed the medical records and pathological slides of 23 patients with malignant phyllodes tumors that had undergone surgical treatment from 1988 to 2006. The age of the patients, tumor size, type of surgery, resection margin, adjuvant therapy and pathological characteristics of the tumors such as stromal hypercellularity, cellular phleomorphism, mitosis, margins, and stromal pattern were examined. Results: The mean age of the patients was 41 yr. The tumor size ranged from 1 cm to 25 cm, with a median of 7.42 cm. The median follow-up time was 29.0 months. Recurrence was observed in 6 patients (26.1%) and the 5-yr disease free survival was 48.9%. Risk factors for recurrence of a malignant phyllodes tumor were a mitotic index greater than 10 per high-powered field (p=0.0242) and an invasive margin (p=0.0437). Conclusion: Frequent mitosis and an invasive margin were the principal determinants of recurrence. Patients with poor prognostic components should be treated more aggressively and the patients need more close follow-up.

Purpose: The purpose of this study was to establish a quality standard for mammographic equipment in Korea and to eventually improve mammographic quality in clinics and hospitals throughout Korea by educating technicians and clinic personnel. Materials and Methods: For the phantom test and on site assessment, we visited 37 sites and examined 43 sets of mammographic equipment. Items that were examined include phantom test, radiation dose measurement, developer assessment, etc. The phantom images were assessed visually and by optical density measurements. For the clinical image assessment, clinical images from 371 sites were examined following the new Korean standard for clinical image evaluation. The items examined include labeling, positioning, contrast, exposure, artifacts, collimation among others. Results: Quality standard of mammographic equipment was satisfied in all equipment during on site visits. Average mean glandular dose was 114.9 mRad. All phantom image test scores were over 10 points (average, 10.8 points). However, optical density measurements were below 1.2 in 9 sets of equipment (20.9%). Clinical image evaluation revealed appropriate image quality in 83.5%, while images from non-radiologist clinics were adequate in 74.6% (91/122), which was the lowest score of any group. Images were satisfactory in 59.0% (219/371) based on evaluation by specialists following the new Korean standard for clinical image evaluation. Satisfactory images had a mean score of 81.7 (1 S.D.=8.9) and unsatisfactory images had a mean score of 61.9 (1 S.D=11). The correlation coefficient between the two observers was 0.93 (p

Purpose: The goal of this study was to survey the overall quality of mammographic images in Korea. Materials and Methods: A total of 598 mammographic images collected from 257 hospitals nationwide were reviewed in terms of eight image quality categories, namely positioning, compression, contrast, exposure, sharpness, noise, artifacts, and examination identification, and rated on a five-point scale: (1=severe deficiency, 2=major deficiency, 3=minor deficiency, 4=good, 5=best). Failure was defined as the occurrence of more than four major deficiencies or one severe deficiency (score of 1 or 2). The results were compared among hospitals of varying kinds, and common problems in clinical image quality were identified. Results: Two hundred and seventeen mammographic images (36.3%) failed the evaluation. Poor images were found in descending order of frequency, at The Society for Medical Examination (33/69, 47.8%), non-radiology clinics (42/88, 47.7%), general hospitals (92/216, 42.6%), radiology clinics (39/102, 38.2%), and university hospitals (11/123, 8.9%) (p

Purpose: To compare the usefulness of real-time compound US (RCUS) with that of conventional US (CUS) and pulse inversion harmonic (PIH) imaging in the diagnosis of malignant breast tumors. Materials and Methods: In 22 female patients whose mean age was 49 years, we evaluated the RCUS findings of pathologically proven [core biopsy (n=9), mammotome tissue bigpsy (n=10), excisional bispsy (n=3)] malignant breast tumors, comparing them with the findings of CUS and PIH imaging. Evaluation of these masses was in terms of their marginal distinction, internal echogenicity, boundary and posterior echo pattern, relationship with the adjacent lactiferous ductal system, and the presence of necrosis (12/22) and calcification (6/22). Results: In terms of marginal distinction, internal echogenicity, boundary echo patterns, and the relationship with adjacent ductal system, RCUS was superior to both conventional US and PIH Imaging (p

Purpose: To evaluate the radiologic findings of direct invasion of the spleen by malignant tumors of adjacent organs. Materials and Methods: We retrospectively reviewed the CT(n=6) and MR(n=3) images of six patients with direct invasion of the spleen by malignant tumor of left lower lung, stomach, colon, pancreas, left kidney, and left adrenal gland. We evaluated the tumor margin, attenuation or intensity, perisplenic fat infiltration, regional lymphnode enlargement, and invaded site of the spleen. Results: Ill-defined masses were found in the spleen with central necrosis and infiltration into perisplenic fatty tissue in all six patients; left adrenal mass was present also in three patients. Regional lymphnode enlargement was found in four patients. The masses showed heterogenous low attenuation on CT. The invaded site was variable and corresponding to their anatomical connections to the spleen. Conclusion: Direct invasion of the spleen by malignant tumors of adjacent organs showed ill-defined masses with central necrosis and were commonly associated with infiltration to perisplenic fatty tissue and adrenal invasion. The pattern and invaded site can be helpful to assess the primary cancer.

Purpose : To compare the radiologic findings of pyogenic abscess(PA) and inflammatory cancer(IC) of the breast, as seen on mammograms, US, and MR images and to evaluate the usefulness of the differential diagnostic findings of MRI for differentiation of PA and IC of the breast. Materials and Methods : We retrospectively analyzed the mammographic, US and MR findings of nine histopathologically proven cases of PA and four cases of IC of the breast. Parenchymal density, mass density, skin thickening and calcification were evaluated by mammography, and the extent of lesion and its morphologic characteristics and changes of dermal lymphatics by US and MRI. The latter was also used to analyse signal intensity and enhancement pattern. Results : Mammographic findings for both lesions were non-specific. US showed that the pyogenic abscess was a hypoechoic and anechoic complex lesion with posterior acoustic enhancement, while inflammatory cancer was a spiculated lesion with a heterogeneous hypoechoic echotexture. On 3D-GRE dynamic enhanced MRI, PA was shown in six cases(66.7 %) to be a lesion with superficial periareolar involvement, in contrast to the deep parenchymal spread seen in all cases of IC. A central non- enhanced portion with an irregular thick peripheral enhanced rim was seen in eight cases of PA(88.9 %) , and in all cases of IC an inhomogeneously enhanced spiculated lesion in parenchyma and a diffusely enhanced dermal and subcutaneous layer was apparent. An MRI time-intensity curve showed that the enhancement pattern was slow in five cases of PA(55.6 % ) and irregular in four(44.4 %), while for IC it was rapid in three cases(33.3 %) and irregular in one(11.1 % ). Conclusion : As compared with mammography and US, 3D-GRE dynamic MRI was a useful method for the differential diagnosis of PA and IC of the breast. The characteristic MR findings of PA were a central non-enhanced portion with an irregularly thick peripheral enhanced rim, located mainly in the superficial periareloar area and spreading into the parenchymal layer. An inhomogeneously enhanced spiculated solid mass in the parenchyma associated with diffuse dermal thickening and lymphatic dilatation was more suggestive of IC.

Purpose : To evaluate the usefulness of MR imaging in the differential diagnosis of the underlying causes of early-stage acute renal failure (ARF) by comparing the MRI findings of experimentally-induced crescentic glomerulonephritis (CGN) and acute tubular necrosis (ATN) in rabbits. Materials and Methods : Experimental CGN was induced by injecting anti-glomerular basement membrane antibody into six rabbits, and ATN by injecting glycerol solution into six rabbits. A normal control group of three rabbits was also used. Renal MR imaging (T1-and T2-weighted coronal images and dynamic MRI : DMRI) was performed the day before, and one, four, and seven days after the induction of CGN; and immediately before, and four, and eight hours, and one, four, and seven days after the induction of ATN. Sequential renal gun-biopsies and blood sampling (serum creatinine, sCr) were performed. Renal area, corticomedullary differentiation(CMD), and the passage of Gd-DTPA (pattern of dark band), as seen on MRI, were analyzed and correlated with serial change of sCr. Results : In normal kidneys, CMD was clearly apparent on both T1- and T2-weighted images. DMRI demonstrated a progressively inwardly migrating dark band in the kidneys. CMD was relatively clearly demonstrated in the ATN group but less clearly identified in the CGN group. Renal size (area) and sCr gradually increased in both the CGN and ATN groups, and dark bands were moderately to poorly defined in both. Conclusion : We conclude that DMRI could be used to differentiate and evaluate disease processing and compromised renal function in cases of CGN and ATN. On T1- and T2-weighted images, CMD was relatively well preserved in the ATN group, but was less clear in the CGN group. These MRI findings may be helpful for differentiation of the underlying causes of early-stage ARF, particularly between CGN and ATN.

Purpose : To clarify the distribution of joint effusion, and the relationship between type of injury andamount of joint effusion seen in traumatic knee joint magnetic resonance imaging (MRI). Materials and Methods : Weretrospectively reviewed the MR images of 400 patients with traumatic knee joint effusion. The knee joint spacewas divided into four compartments: central portion (para-ACL, para-PCL), suprapatellar pouch, posterior femoralrecess, and subpopliteal recess, and we then compared the amount and distribution of effusion. For statisticalanalysis, the chi-square test was used. Results : Among 400 MRI examinations of joint effusion, 383 knees (96%)showed homogeneous low intensity on T1-weighted images, and - except for ten cases of fluid-fluid levels-homogeneous high intensity on T2-weighted images. Knee joint effusion was clearly shown to be distributed mainlyin the suprapatellar pouch (345, 86%), followed by the central posterior femoral recess, and the subpoplitealrecess (P

Localized fibrous tumor of the scrotum is a very rare disease, and few radiologic features have been report-ed. We report the sonographic and CT findings of a case of localized fibrous tumor, which developed in the scrotum of a thirty-years-old man.