PURPOSE: We aimed to investigate the effectiveness of ferritin as a contrast agent and a potential reporter gene for tracking tumor cells or macrophages in mouse cancer models. MATERIALS AND METHODS: Adenoviral human ferritin heavy chain (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images were acquired before and daily for up to 6 days after the intracranial injection of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and every two days after intravenous injection of ferritin-labeled macrophages. The contrast effect of ferritin in vitro was measured by MR imaging of cell pellets. MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted (T2*w) fast low angle shot sequence. RESULTS: Cell pellet imaging of Ad-hFTH in vitro showed a strong negatively enhanced contrast in T2w and T2*w images, presenting with darker signal intensity in high concentrations of Fe. T2w images of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity around or within the Ad-hFTH tumor, which was distinct with time and apparent in T2*w images. After injection of ferritin-labeled macrophages, negative contrast enhancement was identified within the tumor. CONCLUSION: Ferritin could be a good candidate as an endogenous MR contrast agent and a potential reporter gene that is capable of maintaining cell labeling stability and cellular safety.
Animals ; Brain Neoplasms/*diagnostic imaging/pathology ; Cell Line, Tumor ; Cell Tracking/*methods ; Colonic Neoplasms/*diagnostic imaging/pathology ; *Contrast Media/administration & dosage ; Disease Models, Animal ; Female ; *Ferritins/administration & dosage ; Genes, Reporter ; Glioma/*diagnostic imaging/pathology ; Humans ; Injections, Intravenous ; Macrophages ; Magnetic Resonance Imaging/*methods ; Male ; Mice ; Neoplasm Transplantation ; Skin Neoplasms/*diagnostic imaging/pathology ; Time Factors

BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancers (NSCLCs) have emerged as a key predictive biomarker for EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment and should be the primary standard for selecting patients for first-line treatment with EGFR-TKIs. This retrospective study evaluated the ability of direct DNA sequencing to predict the EGFR-TKI response. METHODS: We sequenced exons 18-21 of the EGFR tyrosine kinase domain from genomic DNA isolated from 122 NSCLCs, using paraffin-embedded tissues or cytological specimens. Mutation status was compared with clinicopathological features. Clinical outcomes were assessed based on EGFR genotypes. RESULTS: EGFR gene mutations were identified in 36 patients. EGFR mutations were significantly more frequent in non-smokers or light smokers than in heavy smokers (44.8% vs. 10.9%, p < 0.001) and in females than in males (41.8% vs. 19.4%, p = 0.007). The response rate to EGFR-TKIs in patients with an EGFR mutation was 42.1% (8/19), in contrast to 18.9% (7/37) in patients without a mutation (p = 0.064). Patients with an EGFR mutation had significantly prolonged progression-free survival (8.5 vs. 1.5 months; p = 0.003) and overall survival (40.0 vs. 13.3 months; p = 0.006) with EGFR-TKI treatment, compared with patients without a mutation. Among the 15 patients who responded to EGFR-TKIs, 46.7% (7/15) had wild-type EGFR by the direct sequencing method. CONCLUSIONS: EGFR-TKIs conferred substantial clinical benefit in patients with NSCLCs and EGFR mutations. Detection of an EGFR mutation currently relies on direct sequencing, which cannot be performed on small diagnostic specimens, and the method lacks sensitivity. Sensitive assays are needed to detect EGFR mutations in routine clinical samples.
Carcinoma, Non-Small-Cell Lung ; Disease-Free Survival ; DNA ; Exons ; Female ; Genes, erbB-1 ; Humans ; Light ; Lung Neoplasms ; Male ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Sequence Analysis, DNA

PURPOSE: Obesity-related leptin and leptin receptor (OBR) have a relation to the development of cancer and metastasis and also the low survival rate for breast cancer patients. Leptin has been associated with increased aromatase activity and it displays functional cross-talk with estrogen. This study was designed to determine the relationship between the expression of leptin and OBR in breast cancer tissue and the prognosis of early-stage breast cancer patients, and especially for the tamoxifen-treated patients. MATERIALS AND METHODS: Ninety-five patients with early-stage breast cancer and who had undergone surgical treatment at Kyung Hee University Hospital between January 1994 and June 2004 were analyzed. The surgical specimens underwent immunohistochemical analysis for leptin and OBR. The patients' survival and clinical characteristics were obtained from the medical records. RESULTS: Of the 95 patients, 79 (83%) and 32 (33.7%) showed the expression of leptin and OBR in breast cancer tissue, respectively. The expression of leptin and OBR in breast cancer tissue was not significantly related to the clinicopathological characteristics, including obesity, the expression of hormonal receptor, the HER-2/neu expression, menopause, stage and the nuclear grade. The expression of leptin and OBR was not significantly related to the overall disease-free survival (DFS). For the tamoxifen-treated postmenopausal obese patients, the DFS of the leptin-positive group was higher than that of the leptin-negative group (p=0.017). CONCLUSION: The expression of leptin and OBR in breast cancer tissue may be not a prognostic factor for disease-free survival of breast cancer patients. In the future, further studies are needed to determine whether leptin expression could be a predictive factor for tamoxifen therapy in the postmenopausal obese subgroup among the early breast cancer patients.
Aromatase ; Breast Neoplasms ; Breast* ; Disease-Free Survival ; Estrogens ; Female ; Humans ; Leptin* ; Medical Records ; Menopause ; Neoplasm Metastasis ; Obesity ; Postmenopause ; Prognosis* ; Receptors, Leptin* ; Survival Rate ; Tamoxifen

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common form of mesenchymal tumor of the gastrointestinal tract. Recently, tyrosine kinase inhibitors have improved the treatment of GISTs, and their diagnosis facilitated by immunohistochemical markers. The aim of this paper was to study the clinicopathological features of GISTs of the stomach and determine the accuracy of a new grading system and the prognostic factors. METHODS: Patients with mesenchymal tumors of the stomach, operated on between 1982 and 2004, were identified using medical and pathological files. Immunohistochemical staining for KIT (CD117), CD34, smooth muscle actin (SMA), desmin and s-100 protein were performed, and the diagnoses reviewed. Cases were classified into either the very low, low, intermediate or high risk groups according to National Institutes of Health (NIH) consensus symposium. RESULTS: 78 mesenchymal tumors were reanalyzed, and with the supportive use of immunohistochemical markers, 71 (91%) of the gastrointestinal mesenchymal tumors were shown to be GISTs. The tumors often coexpressed KIT and CD34 (90%) and were variably positive for SMA (18%), s-100 protein (11%) and desmin (23%). With a median follow-up of 73.9 months (range 1~228 months), a recurrence occurred in 10 (14%) patients. Analyses demonstrated that the mitotic index (P<0.001) and tumor size (P<0.001) were significant prognostic factors for survival. The new grading system showed a significant difference between the risk groups and the survival rates (P<0.001). CONCLUSION: Immunohistochemical staining is needed to distinguish GISTs from other mesenchymal tumors. The tumor size and mitotic count are significant prognostic factors for GISTs. The new grading system (2001 NIH) for classifying the 4 risk groups of GISTs, according to the tumor size and the mitotic count, is useful in the evaluation of the tumor behavior.
Actins ; Consensus ; Desmin ; Diagnosis* ; Follow-Up Studies ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Humans ; Mitotic Index ; Muscle, Smooth ; National Institutes of Health (U.S.) ; Prognosis* ; Protein-Tyrosine Kinases ; Recurrence ; S100 Proteins ; Stomach* ; Survival Rate

PURPOSE: The usefulness of focused abdominal sonography for trauma (FAST) is now included in the frame work of the advanced trauma life support for examination of thoraco- abdominal trauma. Ultrasonographic screening is controversial in patients with hollow viscus injury. The purpose of this study is to determine the characteristics of emergency trauma sonographic findings in patients with hollow viscus injury. METHODS: All patients with isolated viscus injury after blunt abdominal trauma were retrospectively enrolled in this study during the 5-year period from December 1997 to November 2002. The patients were screened by using ultrasonography and an underwent explolaparotomy. The patients were diagnosed with a hollow viscus injury based on the surgical findings. Patients with viscus injury combined with parenchymal organ injury after abdominal trauma were excluded. Ultrasonographic examinations were performed by the experienced emergency physicians during the trauma resuscitation. RESULTS: Sixty patients were included in this study. The most common injury site was jejunum (23.3%). The common findings of emergency trauma sonography were free fluid collection (56.7%), none of fluid collection (38.3%), free air and fluid collection (3.3%), and free air (1.7%). The presence of mesenteric injury was significantly associated with fluid collection (x2=0009). CONCLUSION: The most common sonographic findings in hollow viscus injury patients after blunt abdominal trauma are free intraperitoneal fluid (anechoic or mixed echo pattern), normal, and free air (reverberation) in that order. Massive intraperitoneal fluid is more often detected in patients who have a viscus injury combined with a ruptured mesenteric vessel.
Abdominal Injuries ; Advanced Trauma Life Support Care ; Emergencies ; Humans ; Intestines ; Jejunum ; Mass Screening ; Resuscitation ; Retrospective Studies ; Ultrasonography ; Wounds, Nonpenetrating

BACKGROUND/AIMS: The long-term results of Roux-en-Y procedure as a treatment for choledochal cyst or cholelithiasis were compared and analyzed. METHODS: A retrospective analysis was carried out for 70 patients (38 type 1 or type 4A choledochal cysts, 33 cholelithiasis) with ages ranging from 17 to 74 years who had undergone hepaticojejunostomy or choledochojejunostomy in a Roux-en-Y manner, with or without hepatectomy. RESULTS: Late complications related to the surgical procedure include cholangitis, recurrent stone, malignancy, abscess, and peptic ulcer disease. The late complication rate was 37.8% in the choledochal cyst group, and 27.3% in the cholelithiasis group. Cholangitis were found in 8.1% of the choledochal cyst group, and in 12.1% of the cholelithiasis group. Recurrent stones were found in 10.8% and 18.2%, respectively. A malignant tumor was found in each group, and both of them were not resectable. Peptic ulcers or erosions were found in 5 patients (13.5%) of the choledochal cyst group, but no one in the cholelithiasis group (p=0.056). CONCLUSION: Late complications after Roux-en-Y procedure in choledochal cyst or cholelithiasis are not uncommon and relatively serious. Long-term follow-up for the patients is mandatory, with attention being given to not only biliary symptoms, but also symptoms related to peptic ulcer disease.
Abscess ; Cholangitis ; Choledochal Cyst* ; Choledochostomy ; Cholelithiasis* ; Follow-Up Studies ; Hepatectomy ; Humans ; Peptic Ulcer ; Retrospective Studies

BACKGROUND:Even though it is well known that pulmonary rehabilitation (PR) improves exercise capacity, and the quality of life, in patients with chronic lung disease, not many patients can attend hospital based intensive PR in Korea. The purpose of this study was to develop a method for a home-based PR program, and study its effectiveness. METHODS:Twenty patients with chronic lung diseases were randomly divided into two groups : a home PR group comprising of 10 male patients, with a mean age of 70 years, and a control group comprisiong of 10 male patients, with a mean age of 65 years. We developed exercise programs, depending on the exercise capacity of each patient, which were easy to do at home. The PR program consisted of a 12 week period of enforced aerobic (mostly walking) and muscle strengthening exercises, as prescribed by the exercise specialist, in accordance with the functional capacity of the patient. In addition to the education, nutritional and psychiatric consultation was undertaken, and respiratory muscle training arranged. Patients visited hospital every 2 weeks for evaluation and exercise prescription. RESULTS: All patients finished the 12 week course of therapy. Following the home PR, the endurance times and work capacity of the upper and lower extremities were significantly increased in the treatment group in comparison to the controls. The six minute working (Eds note : should) 'working' read 'walking'?) distance was increased from 465+/-60m to 508+/-37m and the maximal inspiratory pressure from 72.8+/-27.2cmH2O to 91.4+/-30.9 cmH2O. The quality of life, as assessed by St Georges Respiratory Questionnaire (SGRQ), was also improved following PR. (Eds note : do you have figures for before and after, and a reference for the SGRQ? i.e. for the main paper.) CONCLUSION: The home PR program we developed seemed to be applicable, and effective, to most of the patients with chronic lung diseases in the study.
Breathing Exercises ; Education ; Exercise ; Humans ; Korea ; Lower Extremity ; Lung Diseases* ; Lung* ; Male ; Prescriptions ; Quality of Life ; Surveys and Questionnaires ; Rehabilitation* ; Specialization

BACKGROUND:Even though it is well known that pulmonary rehabilitation (PR) improves exercise capacity, and the quality of life, in patients with chronic lung disease, not many patients can attend hospital based intensive PR in Korea. The purpose of this study was to develop a method for a home-based PR program, and study its effectiveness. METHODS:Twenty patients with chronic lung diseases were randomly divided into two groups : a home PR group comprising of 10 male patients, with a mean age of 70 years, and a control group comprisiong of 10 male patients, with a mean age of 65 years. We developed exercise programs, depending on the exercise capacity of each patient, which were easy to do at home. The PR program consisted of a 12 week period of enforced aerobic (mostly walking) and muscle strengthening exercises, as prescribed by the exercise specialist, in accordance with the functional capacity of the patient. In addition to the education, nutritional and psychiatric consultation was undertaken, and respiratory muscle training arranged. Patients visited hospital every 2 weeks for evaluation and exercise prescription. RESULTS: All patients finished the 12 week course of therapy. Following the home PR, the endurance times and work capacity of the upper and lower extremities were significantly increased in the treatment group in comparison to the controls. The six minute working (Eds note : should) 'working' read 'walking'?) distance was increased from 465+/-60m to 508+/-37m and the maximal inspiratory pressure from 72.8+/-27.2cmH2O to 91.4+/-30.9 cmH2O. The quality of life, as assessed by St Georges Respiratory Questionnaire (SGRQ), was also improved following PR. (Eds note : do you have figures for before and after, and a reference for the SGRQ? i.e. for the main paper.) CONCLUSION: The home PR program we developed seemed to be applicable, and effective, to most of the patients with chronic lung diseases in the study.
Breathing Exercises ; Education ; Exercise ; Humans ; Korea ; Lower Extremity ; Lung Diseases* ; Lung* ; Male ; Prescriptions ; Quality of Life ; Surveys and Questionnaires ; Rehabilitation* ; Specialization

BACKGROUND: Recent technological developments have introduced a new method to identifying M. tuberculosis complex DNA in clinical samples directly. The direct amplification test (DAT) is approved for identifying M. tuberculosis complex in respiratory specimens that are smear-positive for acid-fast bacilli (AFB). When there is a discrepancy between the AFB smear and DAT, no information on their clinical utility is currently available. In this study, the diagnostic reliability of DAT was investigated in suspected pulmonary tuberculosis patients whose sputum AFB smear was negative. METHODS: From June 1, 1998 through May 30, 1999, 909 patients with presumed active pulmonary tuberculosis were enrolled. A sputum AFB stain, culture, DAT and /or biopsy were performed. using the criteria of clinical tuberculosis or confirmed tuberculosis, the positive predictive value of DAT in diagnosing pulmonary tuberculosis was investigated. RESULTS: The positive predictive value of DAT was 82.1% by the clinically active tuberculosis criteria. However, it decreased to 61.5% when diagnosis was restricted to only to culture positive or biopsy proven cases. The false positive rate of DAT was 18.0%. CONCLUSION: The DAT is a valuable diagnostic method in suspected patients whose sputum AFB is was negative.
Biopsy ; Diagnosis* ; DNA ; Humans ; Polymerase Chain Reaction* ; Sputum* ; Tuberculosis ; Tuberculosis, Pulmonary*

BACKGROUND: Since the advent of AIDS, tuberculosis has become a major public health problem in the western society. Therefore, it is essential that pulmonary tuberculosis be rapidly diagnosed. Light microscopic detection of acid-fast organisms in sputum has traditionally been used for rapidly diagnosing tuberculosis. However positive smears are only observed in about one-half to three-quarters of cases. Studies using PCR for diagnosing pulmonary tuberculosis disclosed several shortcomings suggesting an inability to distinguish between active and treated or in active tuberculosis. In this study, the clinkcal significance of a PCR-bases rapid technique for detecting Mycobacterium tuberculosis DNA in peripheral blood investigated. MATERIALS AND METHODS: From July 1, 1998 through to August 30, 1999, 59 patients with presumed tuberculosis, who had no previous history of anti-tuberculosis medication use whithin one year prior to this study were recruite and followed up for more than 3 months. AFB stain and culture in the sputum and/or pleural fluids and biopsies when needed were performed. Blood samples from each of the 59 patients were obtained in order to identify Mycobacterium Tuberculosis DNA by a PCR test. RESULTS: 1) Forty five out of 59 patients had a final diagnosis of tugerculosis; Twenty eight were confirmed as having active pulmonary tuberculosis by culture or biopsy. Four were clinkcally diagnosed with pulmonary tuberculosis. The othe 13 patients were diagnosed as having tuberculous pleurisy (9) and extrapulmonary tuberculosis (4). 2) Fourteen patients showed a positive blood PCR test. The PCR assay correctly identified active tuberculosis in 13 out of 14 patients. The overall sensitivity and specificity of this blood PCR assay for diagnosing tuberculosis were 29% and 93%, respectively. The positive predictive value was 93%, the negative predictive value was 29% and diagnostic accuracy was 44%. 3) Six out of 14(43%) patients with blood PCR positive tuberculosis were immunologically compromised hosts. 4) A simple chest radiograph in blood PCR positive tuberculosis patients showed variable and inconsistent findings. CONCLUSION: A peripheral blood PCR assay for Mycobacterium tuberculosis is not recommended as screening method for diagnosing active tuberculosis. However, it was suggested that the blood PCR assay could contribute to an early diagnostic rate due to its high positive predictive value.
Biopsy ; Diagnosis ; DNA* ; Humans ; Mass Screening ; Mycobacterium tuberculosis* ; Mycobacterium* ; Polymerase Chain Reaction ; Public Health ; Radiography, Thoracic ; Sensitivity and Specificity ; Sputum ; Tuberculosis ; Tuberculosis, Pleural ; Tuberculosis, Pulmonary