[Show abstract][Hide abstract] ABSTRACT: Brush cytology during ERCP can provide a pathologic diagnosis in malignant biliary obstruction. K-ras and p53 mutations are commonly found in biliary and pancreatic cancers. We evaluated the diagnostic yield of brush cytology and the changes obtained by adding p53 and K-ras staining.
One hundred and forty patients with biliary obstruction who underwent ERCP with brush cytology during a 7-year period were included. The sensitivity and specificity of brush cytology only and with the addition of p53 and K-ras staining were obtained.
Malignant biliary obstruction was confirmed in 119 patients. The sensitivity and specificity of brush cytology were 78.2% and 90.5%, respectively. The sensitivity of cytology was 77.3% at the ampulla-distal common bile duct (CBD), 92.6% at the mid common hepatic duct (CHD), and 94.7% at the proximal CBD-CHD (p<0.05); these values did not differ with the degree or the length of the obstruction. In the 97 patients who received additional p53 and K-ras staining, the sensitivity of cytology plus p53 was 88.2%, cytology plus K-ras was 84.0%, and cytology plus p53 and K-ras was 88.2%. The sensitivity of cytology plus p53 was higher than that of brush cytology only (95% confidence interval: 83.69-92.78 vs 72.65-83.65) but not that of cytology plus K-ras.
Brush cytology for malignant biliary obstruction has a high diagnostic accuracy. Adding p53 staining can further improve the diagnostic yield, whereas K-ras staining does not.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to define the clinical, biochemical, and pathological characteristics of myopathy developed during clevudine therapy.
We prospectively enrolled 36 consecutive myopathy patients who were receiving clevudine therapy for the treatment of chronic hepatitis B (CHB). We evaluated patients with a complete medical history, neurologic examination with a questionnaire on neuromuscular diseases, laboratory tests, electrophysiology studies, and muscle biopsies.
The median duration of clevudine therapy was 18.0 months (ranging from 9 to 24 months). The chief complaint was weakness of the lower extremities in 30 patients (83.3%) and asthenia in five patients (13.9%). One patient (2.8%) had only persistently elevated serum muscle enzyme without any symptoms. Weakness of the lower extremity mainly involved proximal muscle group of the lower extremity, characterized by difficulty in climbing stairs (83.3%), a decrease in exercise capacity (75.0%) and difficulty in walking (55.6%). All patients showed an elevation of more than two of serum creatine kinase, lactate dehydrogenase, and lactate levels. Muscle biopsies performed in 23 patients revealed myopathic features with abnormal mitochondria in 21 patients, and nonspecific myositis in two patients. Motor weakness gradually improved after discontinuation of clevudine.
Myopathy associated with clevudine is characterized by a weakness in proximal muscles of the lower extremities with elevated muscle enzymes and presumably caused by mitochondrial toxicities. Careful medical and serologic examinations are essential for the early detection and management of this potential adverse reaction in CHB patients under clevudine therapy.
No preview · Article · Apr 2010 · Journal of Hepatology
[Show abstract][Hide abstract] ABSTRACT: Background : Making the diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) is often difficult, and there are no accurate immunohistochemical or molecular markers. The purpose of this study is to evaluate performing immunohistochemistry to make the diagnosis of FVPTC. Methods : A total of 249 thyroid lesions were studied. We made the tissue microarray, and we assessed the expression of HBME-1, galectin-3, CD56, and p63. Results : Galectin-3, HBME-1, and p63 were positive in 79.7%, 79.7%, and 15.9% of the FVPTC, respectively. These immunohistochemical features of FVPTC were between those of classic papillary thyroid carcinoma (CPTC) and those of non-PTC. The CD56 expression was positive in 75.4% of the FVPTC, which is much higher than that of the CPTC (28.3%), and even higher than that of the non-PTC lesions (60%). Comparing FVPTC with CPTC, the expression of galectin-3 was significantly higher and the expression of CD56 was significantly lower in the CPTCs. Comparing the FVPTC with follicular carcinoma (FC), the expression of all the markers was significantly higher in the FVPTC. Comparing PTC with FC, the expression of CD56 was lower and the expressions of the other markers were higher in the PTCs. Conclusions : Galectin-3, HBME-1, and p63 can help make the diagnosis of FVPTC, and a cocktail of these markers can be even more useful. But CD56 is not thought to be useful to make the diagnosis of FVPTC.
Preview · Article · Feb 2010 · The Korean Journal of Pathology
[Show abstract][Hide abstract] ABSTRACT: Polymorphisms of genes from glutathione S-transferases (GSTs) and N-acetyltransferase 2 (NAT2) have been associated with increased susceptibility to various cancers. Previous results showed that East Asians such as Koreans, Japanese and Chinese have a much higher frequency of the GSTM1 and GSTT1 null genotypes and NAT2 rapid acetylator type. Therefore, we investigated the association between the polymorphic types of GSTs (GSTM1, GSTT1, GSTP1) and NAT2 and the incidence of gastric cancer which is one of the most prevalent cancers among the East Asians.
It was performed in a case-control study consisting of 238 healthy subjects and 108 cancer patients (54 distal and 54 proximal carcinomas). We also evaluated the association between GSTs and NAT2 and the risk factors for gastric cancer such as alcohol consumption, smoking, H. pylori infection, family history of gastric cancer, and tumor location.
In our study, the percentage of cases whose hometown was rural was higher than those of controls (odds ratio (OR) = 2.88; 95% CI = 1.72-4.76), and the frequency of the lower socio-economic status increased significantly in patients (OR = 2.53; 95% Cl = 1.59-4.02). There was no significant difference in the GST polymorphic types between the cases and controls. However, NAT2 rapid or intermediate acetylator types were frequently detected in the cases with family history of gastric cancer (OR = 1.92; 95% CI = 1.79-26.0).
These results suggest that the hometown and socio-economic status are important environmental factors for gastric carcinogenesis, and NAT2 polymorphic types could be associated with familial gastric carcinoma.
No preview · Article · Apr 2006 · Journal of Preventive Medicine and Public Health
[Show abstract][Hide abstract] ABSTRACT: Acute spinal cord injury (SCI) is two-step process that first involves the primary mechanical injury and then the secondary injury is induced by various biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is thought to play an important role for the delayed neuronal injury. The enhanced formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model. Double-immunofluorescence staining revealed that iNOS positive cells were stained for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) positive cell count was higher for the 72 hr post-SCI group than for the 24 hr post-SCI group. This cell count was also higher going in the caudal direction than in the rostral direction from the epicenter, and especially for the 72 hr group. Treatment with a selective iNOS inhibitor resulted in the reduction of TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes plays an important role for the acute secondary SCI that results from apoptotic cell death.
Preview · Article · Sep 2005 · Journal of Korean Medical Science
[Show abstract][Hide abstract] ABSTRACT: The hypermethylation of the CpG islands is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed the methylation status of genes for cell repair such as hMLH1, MGMT, and GSTP1, and a gastric cancer-specifically methylated DNA fragment, MINT 25 in gastric cancer cases and control groups. The study population consisted of 100 gastric cancer patients (50 distal and 50 proximal carcinomas), and 238 healthy controls. All genes showed more frequent hypermethylation in the cases than in the control group (p<0.0001). We investigated the association between promoter hypermethylation and relevant parameters including age, gender, alcohol consumption, smoking, and family history. There was a common hypermethylation of hMLH1 (p=0.008), MGMT (p= 0.0001), and GSTP1 (p=0.0003) in females. This study also demonstrates that hypermethylation was strongly associated with non-drinkers (MGMT, p=0.046 and MINT 25, p=0.049) and non-smokers (hMLH1, p=0.044; MGMT, p=0.0003; MINT 25, p=0.029). Moreover, the frequency of MINT 25 hypermethylation increased with age (p=0.037), and MGMT methylation was frequently detected in distal gastric cancer than in proximal type (p=0.038). Our study suggested that promoter hypermethylation of the genes involved in cell repair system and MINT 25 is associated strongly with some subgroups of primary gastric carcinoma.
Full-text · Article · Apr 2005 · Journal of Korean Medical Science
[Show abstract][Hide abstract] ABSTRACT: Background : Neuronal death in acute-phase cerebral ischemic injury is caused by necro-sis. However, neuronal injury after reperfusion can be associated with apoptosis. Methods : We used Sprague-Dawley rats whose brains were reperfused after middle cerebral artery occlusion for either 30 min or 2 h. We examined a relationship between apoptosis and the expression of inducible nitric oxide synthase (iNOS) in the brain tissue from 3 h to 14 days after reperfusion in both groups. Results : TUNEL and iNOS positivity were closely related in both groups. The 2-h ischemia group exhibited increases in the amount of TUNEL and iNOS-positive cells for up to 3 days after reperfusion, at which the TUNEL and iNOS-positive cells decreased. The 30-min ischemia group exhibited peak positivity 24 h after reperfusion, fol-lowed by a similar decrease. iNOS mRNA expression peaked 3 h after reperfusion in the 30-min ischemia group, at which time it decreased. In the 2-h ischemia group, iNOS mRNA increased 3 h after reperfusion, peaked 24 h after reperfusion, and then decreased. Conclu-sions : These results indicated the occurrence of delayed apoptosis in transient cerebral ischemia. Increased expression of iNOS is closely associated with this apoptosis, and oxy-gen free radical-producing materials, such as nitric oxide, may play an important role in the induction of this apoptosis.
Preview · Article · Jan 2004 · The Korean Journal of Pathology
[Show abstract][Hide abstract] ABSTRACT: The Neuropathology Study Group of the Korean Society of Pathologists conducted a nationwide collection of central nervous system (CNS) tumors to evaluate the relative frequency in Korea of CNS tumors belonging to the revised World Health Organization (WHO) classification categories. A total of 3221 histologically proven cases of CNS tumors were collected from 13 institutes between 1997 and 1998. All the cases were classified according to the revised WHO histological types and analyzed for the relative frequency, the distribution of age and sex, and location of tumors. The most frequent type of CNS tumors in Korea was meningiomas, followed by pituitary adenoma, glioblastoma, astrocytoma, and schwannoma. Among the pediatric CNS tumors, pilocytic astrocytoma, medulloblastoma, craniopharyngioma, germ cell tumors, and ependymomas were common types of tumors. Compared with a previous nationwide study, the rates for neuronal/glial tumors, glioblastoma, malignant lymphoma, and cystic lesion were increased, and the rate of embryonal tumors was decreased. The overall male to female ratio was 0.9: 1, which may be attributed to the greater number of female-predominate meningiomas and pituitary adenoma. Compared with Western countries, Koreans had higher rates of pituitary adenoma and meningiomas and lower rate of gliomas. The relative frequency of CNS tumors among Koreans is very similar to that reported in Taiwan. The occurrence rates for various subtypes of CNS tumors in Korea are distinct from those in the United States and Europe and similar in many ways to those in Asian and Mexican population.
No preview · Article · Mar 2002 · Journal of Neuro-Oncology
[Show abstract][Hide abstract] ABSTRACT: Hypermethylation of CpG island is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed 13 genitourinary cancer cell lines for aberrant DNA methylation of 5 tumor-related genes using methylation- specific polymerase chain reaction (MSP). GSTP1 was methylated in 5 (38.5%), E-cadherin in 1 (8%), VHL in 1 (8%), and MGMT and hMLH1 in none (0%). Six out of thirteen genitourinary cancer cell lines had methylation of at least one of five genes; 5 had one gene methylated, and, 1 had two genes methylated. Methylation of these 5 genes was not detected in any of the bladder cancer cell lines. GSTP1 was methylated in all of the 3 prostate cancer cell lines. We conclude that aberrant hypermethylation may be an important mechanism for the inactivation of cancer-related genes in kidney and prostate cancer cell lines.
Preview · Article · Jan 2002 · Journal of Korean Medical Science
[Show abstract][Hide abstract] ABSTRACT: Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a progressive cardiac muscle disease characterized as progressive fibrofatty replacement of the right ventricle, severe ventricular arrhythmia, and sudden death. However, there is no report of ARVC as a cause of sudden death in Korea.
[Show abstract][Hide abstract] ABSTRACT: Inactivation of the p16INK4a gene by mutation and deletion is common in head and neck squamous cell carcinoma (HNSCC). The present study demonstrates that hypermethylation of the 5' CpG islands can serve as an alternative mechanism for the inactivation of the p16INK4a gene in this tumor. We studied 11 HNSCC cell lines and 17 oral squamous cell carcinoma (OSCC) primary tumors for p16INK4a gene status by protein/mRNA and DNA genetic/epigenetic analyses to determine the incidence of its inactivation. Our study indicates that: (1) inactivation of p16 protein is frequent in HNSCC cell lines (6/11, 54.5%) and OSCC primary tumors (15/17, 88.2%), (2) inactivation of p16INK4a protein is commonly associated with the presence of gene alteration such as mutation, homozygous deletion and especially aberrant methylation, and (3) genomic sequencing of bisulfite-modified DNA shows that the carcinoma develops a heterogeneous pattern of hypermethylation.
No preview · Article · Nov 2000 · Molecules and Cells
[Show abstract][Hide abstract] ABSTRACT: Described here is a case of accidental intrathecal administration of vincristine with pathologic findings in the central nervous system. A 3-year-old boy with acute lymphoblastic leukemia, was given his ninth course chemotherapy. Vincristine was accidentally injected intrathecally. The clinical course was rapidly progressive (6-day course) and resulted in death. An autopsy was done. The brain and spinal cord was grossly edematous and congested without any specific feature. Histologically, profound loss of neuron was noted in the spinal cord. Remaining neurons in the spinal cord, particularly anterior horn cells were markedly swollen. The spinal nerves show diffuse axonal degeneration and myelin loss. The upstream portion of the spinal cord (brain stem, cerebellum, cerebrum) showed patchy loss of neurons, especially Purkinje cells and granular cells of the cerebellar cortex. Many neurons showed axonal reaction (chromatolysis) with swelling. Several neurons show intracytoplasmic eosinophilic inclusion body. Myelin loss, axonal swelling and enlargement of perivascular spaces were seen throughout the white matter of central nervous system.
Preview · Article · Jan 2000 · Journal of Korean Medical Science