Jung Kee Chung

Effect of nicotine on human umbilical vein endothelial cells (HUVECs) migration and angiogenesis

The effects of nicotine on vascular endothelial cells have not been completely elucidated. We performed this study to assess the changes in cellular behaviors of human umbilical vein endothelial cells (HUVECs) treated with nicotine. We examined changes in cell count and morphology and assayed cellular migration with Boyden chamber and microcapillary tube formation in a Matrigel matrix following treatment with various concentrations of nicotine. Compared to the control, nicotine stimulated cell proliferation, migration, and tube formation at concentrations similar to those found in smokers. Although there were no specific morphological changes in HUVECs treated with nicotine at the concentration similar to that in smokers, at high concentration (10(-4) M), morphological changes such as cytoplasmic vacuolization and irregular cell shape were observed, which were assumed to be the result of direct cytotoxicity of nicotine. In HUVECs, nicotine enhanced cellular proliferation, migration and angiogenesis in vitro, and thus caused a functional change, not a morphological change at a concentration similar to that in habitual smokers.

Combined endovenous laser treatment and ambulatory phlebectomy for the treatment of saphenous vein incompetence

Objectives The aim of this retrospective study is to assess the safety and effectiveness of endovenous laser treatment (EVLT) combined with ambulatory phlebectomy (AP) as a single procedure for treating saphenous vein incompetence. Methods The study enrolled 148 patients with saphenofemoral or saphenopopliteal junction reflux associated with saphenous vein incompetence and enlarged branch veins. Patients were treated with EVLT (135 great saphenous veins, 41 small saphenous veins) concomitantly with AP as a single procedure. All patients were followed up by clinical assessment and duplex ultrasound at one week and 12 weeks after the procedure. Results No postprocedural deep vein thrombosis and pulmonary embolism occurred. Saphenous vein recanalization rate at three months was 5.7%. Residual varicosities were found in 11.4% of the patients at three months after procedure, but only 2.3% of those required subsequent interventions. Conclusion Combined EVLT and AP could be a safe and effective treatment modality for the saphenous vein incompetence.

Restoration of Patency in Iliofemoral Deep Vein Thrombosis with Catheter-Directed Thrombolysis Does Not Always Prevent Post-Thrombotic Damage

OBJECTIVES To evaluate the long-term results of catheter-directed thrombolysis (CDT) and the feasibility of stent placement for lower extremity deep vein thrombosis (DVT). DESIGN & METHODS Retrospective study of 34 patients (10 men and 24 women, mean age 55, S.D. 13 years) with lower extremity DVT underwent CDT at Seoul National University Hospital from January 1999 to October 2003. Patient characteristics, risk factors of DVT, extent of thrombosis, and short-term and long-term results of CDT and/or stent placement were analysed. RESULTS Mean follow-up times were 47 S.D. 16 months. The primary technical success rate was 97% (complete lysis 68%, partial 29%). During the follow-up periods 11 (32%) patients showed re-thrombosis. Sixteen (47%) of 34 patients showed chronic change of vessels during the follow-up periods. By Cox Proportional Hazard analysis, extent of thrombolysis was a statistically significant factor affecting the freedom of re-thrombosis and chronic change (P=0.008 and P=0.001). Nine (44%) of 21 deployed stents were obstructed, and the overall stent patency at 3 years was 56.7%. The only factor affecting the stent patency was stent length more than 6 cm (P=0.002, HR 13, 95% CI 2.7-59). CONCLUSION Long-term results of CDT are not satisfactory because of the high recurrence rate of DVT and it cannot prevent chronic post-thrombotic damage to the affected vessels despite long-term anticoagulation therapy. Careful long-term surveillance of the venous function is highly recommended after CDT.

Malignancy in renal transplant recipients.

With improved management of infectious and cardiovascular complications of renal transplant recipients, prolonged survival with long-term follow up duration, and increasing age of patients, cancer became an increasingly important cause of morbidity and mortality in transplant patients. Literatures indicate three to fivefold incidence of malignancy in solid organ transplant recipients compared with that of general population. Certain types of malignancy, such as skin cancer, Kaposis sarcoma, lymphoma, cervical, oral and anogenital cancer, hepatocelluar and renal cell carcinoma are particularly reported to be high in incidence. Reduction of immunosuppressive medication is the first step to be considered for the management, especially for virus-associated cancer. The inhibitor of mammalian target of rapamycin(mTORi) suppresses the growth and proliferation of tumors in various animal models, cured Kaposis sarcoma and seems to reduce the incidence of de novo malignancies of renal transplant recipients, and is therefore a valuable option for the management of cancer of these patients without increment of the risk of graft rejection.

Epstein-Barr virus, beta-catenin, and E-cadherin in gastric carcinomas

Activated beta-catenin is suggested to inhibit NF-kappaB activation, and we previously demonstrated that NF-kappaB nuclear positivity was more frequent in Epstein-Barr virus (EBV)-infected gastric carcinomas. It is controversial that beta-catenin and E-cadherin are prognostic markers in gastric carcinomas. To define a relationship between beta-catenin and EBV, and the prognostic value of beta-catenin and E-cadherin, we analyzed in situ hybridization for EBV-encoded small RNAs, beta-catenin, and E-cadherin immunohistochemistry, and clinicophatological features in 111 gastric carcinomas. EBV infection was detected in seven carcinomas (6.3%); none of seven showed beta-catenin nuclear accumulation, and five out of seven revealed beta-catenin membranous loss or cytoplamic expression. Eighty cases (72.1%) showed beta-catenin alteration; i.e., loss of membrane staining in 65 (58.6%), cytoplasmic expression in 35 (31.5%), and nuclear accumulation in 15 (13.5%). E-cadherin alteration was observed in 34 cases (30.6%) and correlated with beta-catenin alteration. On multivariate analysis, the combined immunoexpression group of beta-catenin nuclear accumulation/ E-cadherin alteration and the advanced TNM cancer stage group showed poor patients survival (p<0.05). In conclusion, beta-catenin activation through nuclear accumulation hardly occurred in EBV-infected gastric carcinomas. The combined immunoexpression pattern of beta-catenin and E-cadherin can be used as a prognostic marker in gastric carcinomas.

Whole-Body [18F]FDG PET in the Management of Metastatic Brain Tumours

SummaryBackground To determine its roles in the diagnosis and the systemic evaluation of metastatic brain tumours, whole-body positron emission tomography (PET) using [18F]FDG was performed in 20 consecutive patients. Methods  All patients were thought to be suffering or needing to be differentiated from metastatic brain tumours. Nine patients had multiple brain lesions; six were older and showed a rim-enhancing lesion with surrounding oedema; seven had homogeneously enhancing periventricular lesion(s) on computed tomography (CT) and/or magnetic resonance (MR) imaging, thought to be central nervous system lymphomas. Two patients had skull mass(es) and two patients had a solid mass suspected to be, respectively, a haemorrhagic metastasis and a metastatic malignant melanoma. All of them received whole-body [18F]FDG PET and conventional systemic work-up for metastasis in order to compare the results of the two methods. Results  Metastatic brain tumours were diagnosed on whole-body [18F]FDG PET in eleven patients who had extracranial and intracranial hypermetabolic lesions. In nine of these, a conventional work-up also detected primary lesions which on whole-body [18F]FDG PET were seen to be hypermetabolic foci. Systemic lymph node metastases were detected by whole-body [18F]FDG PET only in two patients and histological diagnosis was possible by biopsy of lymph nodes rather than of brain lesions. In the remaining nine patients who had only intracranial hypermetabolic foci, histological diagnosis was made by craniotomy or stereotactic biopsy. It was confirmed that seven of nine patients were suffering from a primary brain tumour and two from metastatic carcinoma. None of the nine showed evidence of systemic cancer on conventional work-up. Histological diagnoses of the primary brain tumours were four cases of primary central nervous system lymphoma and one each of multifocal glioblastoma, Ewings sarcoma, and cavernous angioma. Patients felt no discomfort during the whole-body [18F]FDG PET procedure and there were no complications. The false negative rate in [18F]FDG PET and in conventional work-up was 15.4% and 30.7% respectively. There were no false positives on either [18F]FDG PET or conventional work-up. Conclusion  It is suggested that whole-body [18F]FDG PET is a safe, reliable, and convenient method for the diagnosis and systemic evaluation of patients thought to be suffering or needing to be differentiated from a metastatic brain tumour.

Expression of cell cycle regulators during smooth muscle cell proliferation after balloon catheter injury of rat artery.

Intimal hyperplasia is defined as the abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) with deposition of extracellular matrix. However, the cell cycle regulatory mechanisms of injury-induced VSMC proliferation are largely unknown. To examine the expression kinetics of cell cycle regulatory factors which is known to be worked positively or negatively, we used rat balloon injury model. Marked induction of proliferating cell nuclear antigen (PCNA), G1/S cyclin-dependent kinase (cdk2), and its regulatory subunit (cyclin E) occurred between 1 and 3 days after balloon arterial injury, and this was sustained for up to 7 days and then declined. However, the induction of the negative regulators, p21 and p27, occurred between 3 and 5 days of injury, peaked after 7 and 14 days and was then sustained. VSMC proliferation after balloon catheter injury of the rat iliac artery is associated with coordinated expression of positive (cdk2, cyclin E and PCNA) and negative (p21, p27) regulators. Cell cycle regulators such as cdk2, cyclin E, p21, p27 may be suitable targets for the control of intimal hyperplasia.

Primary Retroperitoneal Malignant Gastrointestinal Stromal Tumor Mimicking Adrenal Mass.

Gastrointestinal stromal tumor (GIST) is the most common non-epithelial tumor in the gastrointestinal tract. Although GIST occurs mainly in the gastrointestinal tract, it also occurs, rarely, in non-gastrointestinal tract and in this case, it is often named as extra-gastrointestinal stromal tumor (EGIST). We experienced a 68-year-old male patient who had been diagnosed preoperatively with accidentaloma of the left adrenal gland by computed tomography, and finally diagnosed as primary retroperitoneal malignant GIST, postoperatively. The operation was performed via anterior abdominal approach, and complete surgical resection was done for a 7 cm sized retroperitoneal tumor near the left adrenal gland. Primary retroperitoneal malignant GIST was the final pathologic diagnosis and the size of the tumor was 6.5 cm and the mitotic count was 7 per high-power field. Diffuse strong positive staining for c-kit protein, CD34 and negative staining for desmin were observed in a immunohistochemistry test. We report here the unusual case of primary retroperitoneal malignant GIST mimicking adrenal mass.

Parametric image of myocardial blood flow generated from dynamic H215O PET using factor analysis and cluster analysis

Algorithm-based parametric imaging of myocardial blood flow (MBF), as measured by H215O PET, has been the goal of many research efforts. A method for generating parametric images of regional MBF by factor and cluster analysis on H215O dynamic myocardial PET was validated by its comparison with gold-standard MBF values determined invasively using radiolabelled microspheres. Right and left ventricular blood pool activities and their factor images were obtained by the application of factor analysis to dynamic frames. By subtraction of the factor images multiplied by their corresponding values on the factors from the original dynamic images for each frame, pure tissue dynamic images were obtained, from which arterial blood activities were excluded. Cluster analysis that averaged pixels having time-activity curves with the same shape was applied to pure tissue images to generate parametric MBF images. The usefulness of this method for quantifying regional MBF was evaluated using canine experiment data. H215O PET scans and microsphere studies were performed on seven dogs at rest and after pharmacological stress. The image qualities and the contrast of parametric images obtained using the proposed method were significantly improved over either the tissue factor images or the parametric images obtained using a conventional method. Regional MBFs obtained using the proposed method correlated well with those obtained by the region of interest method (r=0.94) and by the microsphere technique (r=0.90). A non-invasive method is presented for generating parametric images of MBF from H215O PET, using factor and cluster analysis.

Limited Feasibility in Endovascular Aneurysm Repair Using Currently Available Graft in Korea

Despite the wide acceptance of endovascular aneurysmal repair in patients with abdominal aortic aneurysm (EVAR), stringent morphologic criteria recommended by manufacturers may preclude this treatment in patients with AAA. The purpose of this study was to investigate how many patients are feasible by Zenith and Excluder stent graft system, which are available in Korea. Eighty-two AAA patients (71 men, mean age 70 yr) who had been treated surgically or medically from January 2005 to December 2006 were included. Criteria for morphologic suitability (MS) were examined to focus on characteristics of aneurysm; proximal and distal landing zone; angulation and involvement of both iliac artery aneurysms. Twenty-eight patients (34.1%) were feasible in Zenith stent graft and 31 patients (37.8%) were feasible in Excluder. The patients who were excluded EVAR had an average of 1.61 exclusion criteria. The main reasons for exclusion were an unfavorable proximal neck (n=34, 41.5%) and problem of distal landing zone (n=25, 30.5%). There was no statistical significance among gender, age or aneurysm size in terms of MS. Only 32 patients (39%) who had AAA were estimated to be suitable for two currently approved grafts by strict criteria. However, even unfavorable AAA patients who have severe co-mobidities will be included in EVAR in the near future. Therefore, more efforts including fine skill and anatomical understanding will be needed to meet these challenging cases.