PURPOSE: This study was performed to investigate whether the E2F1 protein expression can be used as a prognostic factor in clinical breast cancer. METHODS: The expressions of E2F1 and retinoblastoma protein (pRB) were analyzed in 165 lymph node positive breast cancers. All patients underwent adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC) after curative surgery. RESULTS: E2F1 was expressed in 43.6% and pRB was expressed in 46.1%. E2F1 expression was significantly increased in pRB-expressing tumors and was associated with S-phase fraction. By univariate survival analyses, E2F1 expression and ER were the significant prognostic factors for the disease recurrence and patient survival. E2F1 was the only significant prognostic factor for the patient outcome after FAC chemotherapy by multivariate analysis. CONCLUSION: Conclusion The results of the current study indicate that abnormal expression of E2F1 and pRB is prevalent and are intimately associated with each other in clinical breast cancer. A significant association between E2F1 expression and patient survival after FAC chemotherapy mondates a further validation study.
Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Doxorubicin ; Drug Therapy ; Fluorouracil ; Humans ; Lymph Nodes ; Multivariate Analysis ; Prognosis ; Recurrence ; Retinoblastoma Protein

BACKGROUND: Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. OBJECTIVE: Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. METHODS: Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. RESULTS: Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. CONCLUSION: Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment.
Desonide ; Diffusion ; Epidermis ; Glucocorticoids ; Inflammation ; Permeability ; Retention (Psychology) ; Skin ; Steroids

BACKGROUND/AIMS: Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs. METHODS: Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy. RESULTS: HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression. CONCLUSIONS: Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.
Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Apoptosis/drug effects ; Autophagy/drug effects ; Caspase 3/metabolism ; Cell Line, Tumor ; Cell Survival/*drug effects ; Deoxycytidine/analogs & derivatives/pharmacology ; Drug Resistance, Neoplasm/*drug effects ; HSP70 Heat-Shock Proteins/*metabolism ; Humans ; Microtubule-Associated Proteins/metabolism ; Pancreatic Neoplasms/*drug therapy ; Quercetin/pharmacology

Intestinal tuberculosis is a common disease of extrapulmonary tuberculosis. A diagnosis of intestinal tuberculosis is difficult as the symptoms and laboratory findings are not specific for the disease. Intestinal tuberculosis may cause various complications, such as intestinal obstruction, intestinal perforation, intraabdominal abscess, intestinal hemorrhage and fistula formation. A duodenal fistula caused by tuberculosis is an especially rare condition. We experienced a case of intestinal tuberculosis with a duodenal fistula as a complication. The patient was a 25-year-old man that presented with weight loss and diarrhea. Esophagogastroduodenoscopy showed a deep ulcerative lesion on the third portion of the duodenum with a fistula opening. A histological finding revealed granulomatous inflammation with multinucleated giant cells. In addition, the result of a Tb PCR assay was positive. After two months of treatment with the appropriate medication, the symptoms improved and the fistula has closed completely. We report the case with a review of the literature.
Abscess ; Adult ; Diagnosis ; Diarrhea ; Duodenum ; Endoscopy, Digestive System ; Fistula* ; Giant Cells ; Hemorrhage ; Humans ; Inflammation ; Intestinal Obstruction ; Intestinal Perforation ; Polymerase Chain Reaction ; Tuberculosis* ; Ulcer ; Weight Loss

Background/Aims: Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model. Methods: A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined. Results: Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode. Conclusions Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.

Background/Aims: Irreversible electroporation (IRE) is a relatively new ablation method. However, the application of IRE ablation in the treatment of biliary disease has not been attempted. A minimally invasive approach using endoscopic retrograde cholangiopancreatography (ERCP) can be a novel therapeutic modality for IRE ablation. In this study, we aimed to investigate the feasibility of endoscopic IRE for the biliary tract using an animal model. Methods: A new catheter-type electrode was developed for endoscopic IRE ablation of the biliary tract. We performed ERCP and endoscopic IRE ablations in the normal common bile duct of Yorkshire pigs. The experimental setting of IRE was 500 V/cm (50 pulses, 100-µs length). The animals were sacrificed after 24 hr, and the ablated bile duct was examined. Results: Well-demarcated focal color changes were observed on the mucosa of the common bile duct. The depth of change after IRE was confined to the mucosal and submucosal layers. Apoptotic changes in the bile duct were observed only around the IRE ablation area. Immunohistochemistry assay showed cell death in the bile duct along the electrode. Conclusions Endoscopic IRE ablation using ERCP was successfully performed in the common bile duct. It can be a potential option for the treatment of biliary tumors.

Background/Aims: Gastric electrical stimulation (GES) is a feasible modality for the treatment of gastroparesis; however, the presently available device requires invasive surgical implantation for long-term stimulation and repeated surgical procedure after a period of time. This study is aimed at developing a wireless miniature GES device and testing its endoscopic insertion in animal models. Methods: Endoscopic gastric implantation of the GES device was performed on 5 healthy weaner pigs under general anesthesia. We created an endoscopic submucosal pocket and inserted the gastro-electrical stimulator. In vivo gastric slow waves were recorded and measured during electrical stimulation. A multi-channel recorder, called an electrogastrogram, was used to record the gastric myoelectrical activity in the study. Results: The gastric slow waves on the electrogastrogram were more consistent with GES on the gastric tissues compared to no stimulation. The frequency-to-amplitude ratio was also significantly altered after the electrical stimulation. Conclusions GES is feasible with our minimally invasive wireless device. This technique has the potential to increase utilization of GES as a treatment alternative.

BACKGROUND/AIMS: Capsule endoscopy (CE) is a new method enabling noninvasive diagnosis of small bowel diseases. There have been few studies examining the possibility of interobserver variation according to proficiency. We evaluated the interobserver variability between expert and novice for reviewing CE images. METHODS: Among patients who were taken CE from June 2003 to July 2003, twenty patients were randomly selected. Captured images were assessed by an expert and a novice separately. The expert has experience of more than 150 CE interpretation and the novice only had experience in performing EGD and colonoscopy. The novice had trained on interpretation of the CE with 5 cases before this study. Interobserver agreement was evaluated using kappa coefficient. RESULT: CE findings were divided into normal/ abnormal groups. Abnormal groups were classified into small focal, large focal, multiple diffuse, structural deformity groups. Compared with the expert, the novice missed 2 cases (Meckel's diverticulum and angiodysplasia). There was no disagreement in other cases. CONCLUSION: There is 90% (18/20) interobserver agreement between the expert and the novice for the interpetation of findings CE (k=0.737). Normal findings and diffuse large lesions tended to have higher concordance, whereas small focal lesion and structural deformities were more likely to be a source of disagreement.
Capsule Endoscopy* ; Colonoscopy ; Congenital Abnormalities ; Diagnosis ; Diverticulum ; Humans ; Observer Variation

BACKGROUND/AIMS: Since endoscopes are reusable apparatus classified as semicritical item, thorough reprocessing to achieve high-level disinfection is of utmost importance to prevent spread of infection. To improve disinfection efficacy and safety, disinfectants and endoscope reprocessors are continuously evolving. This study aimed to compare the efficacy of the combination of polyhexamethylenebiguanide hydrochloride-alkyldimethylbenzylammonium chloride (PHMB-DBAC) and orthophthalaldehyde (OPA) used respectively in ultrasonographic cleaning incorporated automated endoscope reprocessors: COOLENDO (APEX Korea) or OER-A (Olympus Optical). METHODS: A total of 86 flexible upper endoscopes were randomly reprocessed with either COOLENDO/PHMB-DBAC or OER-A/OPA. Culture samplings were done at two sites (endoscope tip and working channel) which were later incubated on blood agar plate. Bacterial colonies were counted and identified. RESULTS: The culture-positive rate at the endoscope tip and working channel was 0% and 2.33% for COOLENDO/PHMB-DBAC and 4.65% and 0% for OER-A/OPA. Staphylococcus hominis was cultured from one endoscope reprocessed with COOLENDO/PHMB-DBAC and Pseudomonas putida was isolated from two endoscopes reprocessed with OER-A/OPA. CONCLUSIONS: The reprocessing efficacy of COOLENDO/PHMB-DBAC was non-inferior to that of OER-A/OPA (p=0.032; confidence interval, -0.042 to 0.042). During the study period, significant side effect of PHMB-DBAC was not observed.
Agar ; Disinfectants ; Disinfection ; Endoscopes ; Pseudomonas putida ; Staphylococcus hominis

BACKGROUND/AIMS: Terlipressin and somatostatin decrease portal venous pressure and they are used for the treatment of variceal bleeding. However, only a few studies have compared the efficacy of these drugs in combination with other procedures for hemostasis. Therefore, we performed a prospective study to compare the efficacy of terlipressin and somatostatin for controlling acute variceal bleeding when used in combination with other procedures for hemostasis. METHODS: A total of 98 patients, who presented with variceal bleeding from September 2003 to May 2005, were randomly divided into the somatostatin group or terlipressin group. We compared the 5-day failure rate (defined as failure to control bleeding, rebleeding or death within 5 days of admission) and the 6-week mortality. The prognostic factors for 5-day failure and 6-week mortality were also evaluated. RESULTS: There were no differences in baseline characteristics between the two groups. The overall 5-day failure rate and the cumulative 6-week mortality were 16.3% and 15.8%, respectively. The five-day failure rate and the cumulative 6-week mortality were not significantly different between the somatostatin and terlipressin groups. Hepatocellular carcinoma, the baseline serum creatinine level and endoscopic treatment for hemostasis were the significant predictors of 5-day failure; the baseline serum creatinine level was the predictor of 6-week mortality. CONCLUSIONS: Both somatostatin and terlipressin were effective and showed comparable efficacy for the control of the acute variceal bleeding in the setting of a combined therapeutic approach. The baseline serum creatinine level may be a significant predictor for patient failure at 5 days and the 6-week mortality.
Acute Disease ; Aged ; Carcinoma, Hepatocellular/complications ; Esophageal and Gastric Varices/complications/*drug therapy ; Female ; Gastrointestinal Hemorrhage/complications/*drug therapy ; Hemorrhage/complications/drug therapy ; Hemostasis, Endoscopic ; Humans ; Liver/*blood supply ; Liver Cirrhosis/*complications ; Liver Diseases/drug therapy ; Liver Neoplasms/complications ; Lysine Vasopressin/administration & dosage/*analogs & derivatives/therapeutic use ; Male ; Middle Aged ; Multivariate Analysis ; Somatostatin/administration & dosage/*therapeutic use ; Varicose Veins/complications/drug therapy ; Vasoconstrictor Agents/administration & dosage/*therapeutic use