PURPOSE: Since the discovery of estrogen receptor-beta(ER-beta, five C-terminal variants of ER-beta were identified. We designed this study to investigate the pattern and clinical implications of ER-betaand its splicing variants expression in normal and malignant mammary tissues. METHODS: Using reverse transcription polymerase chain reaction (RT-PCR), we examined the expression levels of ER-alpha and ER-betaand its five splicing variants (beta1, beta2, beta3, beta4, beta5) in 50 paired normal and cancer tissues. We measured the densities of RT-PCR products using Tina version 2.10 (Raytest, Germany). Firstly, the incidence and intensity of ER-alpha and ER-beta and its five splicing variants were compared. Then the expression of ER-betamRNA splicing variants was also analyzed with regard to the ER-alphaprotein expression measured by immuno-histochemical staining and the menopausal status of the patients. Chi-square test and paired samples t-test were used for statistical analysis. Differences were considered to be significant with a p-value of less than 0.05. RESULTS: The expression of ER-betamRNA variants in normal breast and cancer tissues were as follows: ER-beta2 (100%/100%), ER-beta4 (76%/74%), ER-beta5 (32%/58%), and ER-beta1 (14%/16%). ER-beta3 was not detected at all. In terms of intensity, we observed a significant decrease of ER-beta2 (P<0.001) and an increase of ER-beta5 (P=0.004) in the mRNA expression levels among breast cancers compared to the corresponding normal breast tissues. Compared to the corresponding normal tissues, a significant decrease of ER-beta2 in cancer tissues was observed in patients with ER-alpha-positive (P<0.001), with age over 50 (P=0.01), and under 50 (P=0.04) as well, but not in patients with ER-alpha-negative (P=0.48). ER-beta4 also significantly decreased in patients with ER-alpha-positive (P=0.004) and with age over 50 (P=0.07). ER-beta5 showed a significant increment only in patient aged over 50 (P=0.04). CONCLUSION: ER-alpha mRNA expression significantly increases but ER-beta mRNA expression decreases in the cancer tissues compared to the corresponding normal tissues. Among ER-beta variant forms, ER-beta2 is predominant in both normal and malignant mammary tissues and ER-beta4, ER-beta5, and ER-beta1 in descending order but ER-beta3 does not express in mammary tissues. The decrease of ER-beta2 and ER-beta4 expression is prominent in cancer tissue especially in ER-alpha-positive cancers, which suggests that ER-beta2 and ER-beta4 may possess a regulatory function in mammary carcinogenesis. Further investigations to verify the roles of ER-beta variants are mandatory.
Breast ; Breast Neoplasms ; Carcinogenesis ; Estrogens* ; Humans ; Incidence ; Polymerase Chain Reaction ; Receptors, Estrogen ; Reverse Transcription ; RNA, Messenger

ERCP is the standard treatment for common bile duct stones. On the other hand, 10-15% of cases involve intractable common bile duct stones, which cannot be treated by conventional biliary sphincterotomy with a stone retrieval method. Large bile duct stones are typically managed by mechanical lithotripsy and endoscopic papillary large balloon dilatation. Peroral cholangioscopy techniques can be applied if this technique fails. In the present case, a 67-year-old woman had a large common bile duct stone that could not be retracted using the conventional ERCP stone extraction method. The common bile duct stone was eventually removed by direct peroral upper gastrointestinal endoscopy and a polypectomy snare.

Background/Aims: Recent reports suggest that the biliary self-expandable metallic stent (SEMS) is highly effective for maintaining hemostasis when endoscopic hemostasis fails in endoscopic retrograde cholangiopancreatography (ERCP)-related bleeding. We compared whether temporary SEMS offers better efficacy than angioembolization for refractory immediate ERCP-related bleeding. Methods: Patients who underwent SEMS placement or underwent angioembolization for bleeding control in refractory immediate ERCP-related bleeding were included in the retrospective analysis. We evaluated the hemostasis success rate, severity of bleeding, change in hemoglobin levels, amount of transfusion, and delay to the start of hemostasis. Results: A total of 27 patients with SEMS and 13 patients who underwent angioembolization were enrolled. More transfusions were needed in the angioembolization group (1.0±1.4 units vs. 2.5±2.0 units; p=0.034). SEMS failure was successfully rescued by angioembolization. The partially covered SEMS (n=23, 85.1%) was generally used, and the median stent-indwelling time was 4 days. The mean delay to the start of angioembolization was 95.2±142.9 (range, 9–491) min. Conclusions Temporary SEMS had similar results to those of angioembolization (96.3% vs. 92.3%; p=0.588). Immediate SEMS insertion is considered a bridge treatment modality for immediate refractory ERCP-related bleeding. Angioembolization still has a role as rescue therapy when SEMS does not work effectively.

Percutaneous endoscopic gastrostomy (PEG) is a common method for providing long-term enteral nutrition to patients. PEG tube placement and removal are relatively safe; generally, a PEG tube can be removed using gentle traction, and excessive bleeding is rare. The over-the-scope clip system is a new device that can be used for gastrointestinal hemostasis and for closing gastrointestinal fistulae. In the present case, a 68-year-old male patient had to remove the PEG tube because of persistent leakage around the PEG tube. Although it was gently removed using traction, incessant bleeding continued, with a Rockall score of 5 points, even after hemocoagulation was attempted. An over-the-scope clip device was used to achieve hemostasis and fistula closure.

Lynch syndrome is a genetic malignancy syndrome affecting the colon, endometrium, and other organs. It is difficult to find a Lynch syndrome patient without any family history of cancer. We have recently examined an endometrial cancer patient with a MSH2 gene mutation without a family history of cancer. A 55-year old Korean woman was admitted to a local clinic for vaginal bleeding. An endometrial biopsy revealed the presence of adenocarcinoma (endometrioid type, grade 1). After surgical staging, no further adjuvant therapy was required. Analysis of the tissue using immunohistochemistry (IHC) showed the endometrium stained negatively for MSH2. Microsatellite instability (MSI) was analyzed for five markers. The patient was scored as unstable. Further, additional gene sequencing revealed one missense mutation in c.23C > T (p.Thr8Met). This is the first case of Lynch syndrome endometrial cancer in Korea in which the patient does not have any family history of cancer.
Adenocarcinoma ; Biopsy ; Colon ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Endometrial Neoplasms* ; Endometrium ; Female ; Germ-Line Mutation* ; Humans ; Immunohistochemistry ; Korea ; Microsatellite Instability ; Middle Aged ; Mutation, Missense ; Uterine Hemorrhage

BACKGROUND/AIMS: Proton pump inhibitor (PPI) and two types of antimicrobial agents, amoxicillin, and clarithromycin have been widely used for the eradication of Helicobacter pylori. However, antibiotic resistant strains has rapidly increased and has emerged as an important factor for eraducation failure. MATERIALS AND METHODS: Patients diagnosed with chronic gastritis, peptic ulcer disease or gastric epithelial neoplasm was examined by H. pylori PCR for mutation at 23S rRNA. Positive H. pylori PCR without 23S rRNA mutation was eradicated by standard triple therapy. Patients with 23S rRNA mutation was eradicated by standard triple therapy or concomittent therapy with amoxicillin, PPI, clarithromycin and metronidazol or quadruple therapy with bismuth, PPI, tetracycline and metronidazol. We evaluated the predictors of eradication failure with regards to 23S rRNA mutation and initial eradication regimen. RESULTS: Nine hundred sixty-one patients were studied. H. pylori PCR was positive in 35.0% of the patients and 23S rRNA mutatation was found in 22.2% of the patients. The eradication rate of H. pylori for the A2143G point mutated group with standard triple therapy was 28.5% and significantly lower than 93.1% of the wild type group and 100% of the concomitant therapy group, 66.6% of one week quadruple group and 100% of two week quadruple group (P<0.005). CONCLUSIONS: When 23S rRNA point mutation was positive, the standard triple therapy was not effective and the eradication rates was only 22.2%. Alternative regimens should be considered when 23S rRNA point mutation is detected, especially when A2143G point mutation is detected because A2143G point mutation is highly related to eradication failure.
Amoxicillin ; Anti-Infective Agents ; Bismuth ; Clarithromycin ; Daegu ; Gastritis ; Helicobacter pylori* ; Humans ; Neoplasms, Glandular and Epithelial ; Peptic Ulcer ; Point Mutation ; Polymerase Chain Reaction ; Proton Pumps ; RNA* ; Tetracycline

Leber's Hereditary Optic Neuropathy(LHON) is a maternally inherited disorders that occurs primarily in young males and is characterized by subacute, sequential, bilateral central visual loss, ultimately, optic atrophy. We report 2 cases of molecularly confirmed LHON which reveal 11778 and 14484 mitochondral DNA mutation, respectively but there is no family history of visual loss. So the diagnosis of LHON deserves to be considered in all crypotogenic cases of acute or subacute optic or chiasmal neuropathy. Late or early age at onset, female gender, and a negative family history should not be dissuasive.
Diagnosis ; DNA ; Female ; Humans ; Male ; Molecular Biology* ; Optic Atrophy ; Optic Nerve Diseases*

Crohn's disease (CD) is a chronic immune-mediated inflammatory disorder. Treatment strategies for CD are targeted toward various components of the proinflammatory mediators and subsequent immune response. Recently, the anti-tumor necrosis factor (TNF) monoclonal antibody, infliximab has been used in patients with CD. However, uncommon and unusual infections have been reported during anti-TNF-alpha therapy and immunomodulator. Here, we report a case of pityriasis versicolor occurring in a patient with CD receiving infliximab treatment. The patient was successfully treated with topical ketoconazole.
Antibodies, Monoclonal ; Crohn Disease ; Humans ; Infliximab ; Ketoconazole ; Malassezia ; Necrosis ; Tinea Versicolor

PURPOSE: Increased level mitogen-activated protein kinase (MAPK) and activation of MAPK have been reported in human breast cancers, especially in breast cancers with HER2/neu overexpression. To understand the relationship between the MAPK protein expressions and other clinico-pathological parameters, we examined the status of MAPKs in 20 breast cancers compared to those of paired normals. METHODS: A total of 20 breast cancers and paired normal breast tissues were included in this study. Tissues were obtained at the operation room and stored at -80degrees C. Tissue proteins were extracted and the concentration was determined by Bio-Rad protein assay method. Western blot analysis were performed to determine the level of MAPKs expressions using 100 ug of tissue protein in 8%, 10%, or 12% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). MAPK assays were carried out by a non-radioactive method developed by Cell Signaling Tech. as recommened by the manufacturer. Clinico-pathological information was provided from the Breast Cancer Registry of Department of Surgery, Yonsei University College of Medicine. RESULTS: The levels of MAPKs were higher in 95% of breast cancers compared to those of paired normals. The levels of ERK1/2 were significantly higher in cancer tissues compared to paired normals but the activated forms were not. The levels of JNK, p38, and MKP1 proteins were significantly increased in the cancer tissue compared to the paired normals. The levels of ERK1/2 and activated ERK1/2 proteins were not different between tumor stages. There were no significant differences of the levels of ERK1/2 and activated ERK1/2 proteins between HER2-negative and HER2- positive cancers. There were significantly higher levels of activated ERK1/2 proteins in ER-positive cancers than those in ER-negative cancers (P<0.05). CONCLUSION: The levels of MAPKs, but not the activated forms, seem to be increased in breast cancer tissues compared to those of paired normals. The levels of activated MAPKs seem to be associated with estrogen receptor expression in cancer tissues.
Blotting, Western ; Breast Neoplasms* ; Breast* ; Carcinogenesis* ; Electrophoresis, Polyacrylamide Gel ; Estrogens ; Humans ; Mitogen-Activated Protein Kinases* ; Protein Kinases ; Sodium

PURPOSE: Estrogen signal transduction plays very important roles in both normal mammary development and neoplastic progression. Since the discovery of estrogen receptor-beta (ER-beta) there have been many controversial reports on the role of ER-beta in breast carcinogenesis and progression, and prognostic implications. ER-beta mRNA levels were investigated in various mammary tissues in order to verify the role of ER-beta expression in breast carcinogenesis. METHODS: Using messenger RNA (mRNA) in situ hybridization, we examined ER-beta expression in 60 paired normal and cancer tissues, 11 paired normal and benign breast tumor tissues, and 10 metastatic lymph nodes. We determined the intensity and extent (proportion of cells with positive hybridization) of the mRNA hybridization signals and gave scores 0 to 3; no hybridization (0), minimal (1), moderate (2), and strong (3) by the hybridization intensity and no hybridization (0), hybridization in less than 10% of cells (1), 10~50% (2), and more than 50% of cells (3) by the proportion of positively hybridized cells. Chi-square test, independent t-test or one-way ANOVA test was used for the statistical analysis and differences were considered to be significant with a p-value of less than 0.05. RESULTS: There was no statistically difference in ER-beta expression between normal and benign mammary tissues. ERbeta expression was significantly decreased in breast cancer and metastatic lymph node tissues compared with normal mammary and benign breast tumor tissues (P<0.01). The intensity and extent of ER beta expression were also significantly lower in breast cancer and metastatic lymph node tissues than in the normal mammary and benign breast tumor tissues (P<0.01). In cases of positive hybridization, the sum of scores of intensity and area were also significantly higher in normal and fibroadenoma tissues than in cancer or metastatic lymph nodes (P<0.01). CONCLUSION: ER beta transcription decreases in the process of breast cancer development, which suggests a protective role of ER beta in breast carcinogenesis.
Breast ; Breast Neoplasms ; Carcinogenesis ; Estrogen Receptor beta ; Estrogens* ; Fibroadenoma ; In Situ Hybridization ; Lymph Nodes ; RNA, Messenger* ; Signal Transduction