Kwang An Kwon

Korea red ginseng on Helicobacter pylori-induced halitosis: newer therapeutic strategy and a plausible mechanism.

Background: Gas chromatographic documentation of volatile sulfur compounds in Helicobacter pylori cultures and the amelioration of halitosis after eradication suggested a causal link between H. pylori infection and halitosis. Aim: We hypothesized that Korea red ginseng can relieve H. pylori-associated halitosis based on their anti-inflammatory and cytoprotective actions in H. pylori-associated gastritis. Methods: Eighty-eight functional dyspepsia patients presenting with either subjective halitosis or objective halimeter levels >100 ppb were recruited, on whom tests were repeated after 10 weeks of red ginseng administration. The expressions of cystathionine γ-lyase (CSE), cystathionine β-synthetase (CBS), IL-6, IL-8 and IL-1β mRNA were compared in H. pylori-infected or NaHS-treated gastric epithelial cells according to red ginseng treatment. Results: After 10 weeks of red ginseng administration, 38 patients out of 68 H. pylori-positive cases became ‘free of halitosis’ accompanied with halimeter levels <50 ppb accordant with the subjective resolution of halitosis. Among the remaining 30 patients, 15 cases administered with both eradication regimen and red ginseng supplement showed either higher eradication rates (93.3%) or were found to be completely free of halitosis in comparison to the other 15 patients who were only administered the eradication regimen. Among 20 H. pylori-negative patients, 13 patients became ‘free of halitosis’ with 10 weeks of red ginseng treatment alone. Red ginseng extracts significantly decreased H. pylori- or NaHS-induced CSE expressions concomitant with attenuated levels of IL-6, IL-8 and IL-1β mRNA. Conclusion: The strategy consisting of Korea red ginseng supplementation after the successful eradication of H. pylori could be an effective way to fight troublesome halitosis.

A comparison of patient acceptance and preferences between CT colonography and conventional colonoscopy in colorectal cancer screening.

BACKGROUND/AIMS Mutations of the epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) are important in the pathogenesis of lung cancer, and recent reports have revealed racial and geographical differences in mutation expression. METHODS This study was conducted to investigate the prevalence of EGFR and KRAS mutations and their correlation with clinical variables in Korean patients with adenocarcinoma of the lung. Formalin-fixed adenocarcinoma specimens from 104 randomly selected patients diagnosed at Kosin University Gospel Hospital from October 1996 to January 2005 were used for the study. RESULTS We found a high prevalence of EGFR mutations and a low prevalence of KRAS mutations. EGFR mutations were present in 24% (25 of 104) of the samples: one mutation in exon 18, 13 in exon 19, one in exon 20, and 10 in exon 21. The presence of an EGFR mutation was not associated with gender, smoking history, histological grade, age, bronchioalveolar components, or cancer stage in patients with adenocarcinoma of the lung. CONCLUSIONS Mutations of KRAS were present in 9.6% (9 of 94) of the samples: eight in codon 12 and one in codon 13. EGFR mutations were never found in tumors with KRAS mutations, suggesting a mutually exclusive relationship.

The efficacy of self-expanding metal stents for malignant colorectal obstruction by noncolonic malignancy with peritoneal carcinomatosis.

BACKGROUND: Although self-expanding metal stents for colorectal obstruction is preferred over emergency surgery, the efficacy of self-expanding metal stents in patients with malignant colorectal obstruction by a noncolonic malignancy with peritoneal carcinomatosis has not been demonstrated. OBJECTIVE: The aim of this study was to evaluate the survival and long-term clinical outcome of self-expanding metal stents as the initial interventional approach in patients with malignant colorectal obstruction due to a noncolonic malignancy with peritoneal carcinomatosis. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at 2 tertiary care academic medical centers in South Korea. PATIENTS: The patients were included who underwent self-expanding metal stent insertion for palliation of a malignant colorectal obstruction by a noncolonic malignancy with peritoneal carcinomatosis between July 2004 and January 2010. Inclusion criteria were incurable status, noncolorectal cancer, obstructive symptoms and/or signs, and colonoscopic findings of obstruction. MAIN OUTCOME MEASURES: The survival and success rate of patients undergoing self-expanding metal stents insertion was assessed. RESULTS: Twenty patients were included during the study period. Technical success of self-expanding metal stents was achieved in 18/20 (90.0%) patients, and obstructive symptoms were resolved within 72 hours in 17/20 (85.0%) patients. Ten patients (10/20, 50%) did not need further intervention during the follow-up period after the first stent insertion. Eight patients ultimately underwent surgery during the follow-up period. One of the remaining 2 patients underwent additional endoscopic treatment without surgery. Another patient refused further intervention and thus received conservative management. Mean event-free survival was 119.0 days, and the mean overall survival of the included patients was 156.3 days. LIMITATION: The number of study patients was small. CONCLUSION: Self-expanding metal stent insertion appears to be a reasonable first-treatment option in patients with malignant colorectal obstruction by noncolonic malignancy with peritoneal carcinomatosis.

Influence of Transforming Growth Factor-β1 Gene Polymorphism at Codon 10 on the Development of Cirrhosis in Chronic Hepatitis B Virus Carriers

Transforming growth factor (TGF)-β1 is a key cytokine producing extracellular matrix. We evaluated the effect of TGF-β1 gene polymorphism at codon 10 on the development of cirrhosis in patients with chronic hepatitis B. One hundred seventy eight patients with chronic hepatitis (CH, n=57) or liver cirrhosis (LC, n=121), who had HBsAg and were over 50 yr old, were enrolled. The genotypes were determined by single strand conformation polymorphism. There were no significant differences in age and sex ratio between CH and LC groups. HBeAg positivity and detection rate of HBV DNA were higher in LC than in CH groups (P=0.055 and P=0.003, respectively). There were three types of TGF-β1 gene polymorphism at codon 10: proline homozygous (P/P), proline/leucine heterozygous (P/L), and leucine homozygous (L/L) genotype. In CH group, the proportions of P/P, P/L, and L/L genotype were 32%, 51%, and 17%, respectively. In LC group, the proportions of those genotypes were 20%, 47%, and 33%, respectively. The L/L genotype was presented more frequently in LC than in CH groups (P=0.017). Multivariate logistic regression analysis confirms that detectable HBV DNA (odds ratio [OR]: 3.037, 95% confidence interval [CI]: 1.504-6.133, P=0.002) and L/L genotype (OR: 3.408, 95% CI: 1.279-9.085, P=0.014) are risk factors for cirrhosis.

Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer

AIM To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition (EMT) in colon cancer. METHODS Human colon cancer HCT116 and HT29 cells were exposed to normoxic (21%) and hypoxic (1%) conditions. First, the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers (Snail, Slug, Twist, E-cadherin, and integrin αVβ6) and hypoxia-related genes [Hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF)] by dexamethasone, quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore, the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally, the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion, migration, and wound healing migration assays. RESULTS Under hypoxia, dexamethasone treatment inhibited HIF-1α protein level and its downstream gene, VEGF mRNA level in the colon cancer cell lines, HCT116 and HT29. In addition, the presence of dexamethasone down-regulated the mRNA levels of hypoxia-induced Snail, Slug, and Twist, all transcriptional factors of EMT, as well as hypoxia-induced integrin αVβ6 protein level, a well-known EMT marker for colon cancer cells. Furthermore, reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly, under hypoxic conditions, dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia. CONCLUSION Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition.

Surgical failure after colonic stenting as a bridge to surgery

AIM To identify risk factors for surgical failure after colonic stenting as a bridge to surgery in left-sided malignant colonic obstruction. METHODS The medical records of patients who underwent stent insertion for malignant colonic obstruction between February 2004 and August 2012 were retrospectively reviewed. Patients with malignant colonic obstruction had overt clinical symptoms and signs of obstruction. Malignant colonic obstruction was diagnosed by computed tomography and colonoscopy. A total of 181 patients underwent stent insertion during the study period; of these, 68 consecutive patients were included in our study when they had undergone stent placement as a bridge to surgery in acute left-sided malignant colonic obstruction due to primary colon cancer. RESULTS Out of 68 patients, forty-eight (70.6%) were male, and the mean age was 64.9 (range, 38-89) years. The technical and clinical success rates were 97.1% (66/68) and 88.2% (60/68), respectively. Overall, 85.3% (58/68) of patients underwent primary tumor resection and primary anastomosis. Surgically successful preoperative colonic stenting was achieved in 77.9% (53/68). The mean duration, defined as the time between the SEMS attempt and surgery, was 11.3 d (range, 0-26 d). The mean hospital stay after surgery was 12.5 d (range, 6-55 d). On multivariate analysis, the use of multiple self-expanding metal stents (OR = 28.872; 95%CI: 1.939-429.956, P = 0.015) was a significant independent risk factor for surgical failure of preoperative stenting as a bridge to surgery. Morbidity and mortality rates in surgery after stent insertion were 4.4% (3/68) and 1.5% (1/68), respectively. CONCLUSION The use of multiple self-expanding metal stents appears to be a risk factor for surgical failure.

Gastric angiodysplasia in a hereditary hemorrhagic telangiectasia type 2 patient.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal-dominantly inherited disease that occurs in approximately one in 5000 to 8000 people. Clinical diagnosis of HHT is made when a person presents three of the following four criteria: family history, recurrent nosebleeds, mucocutaneous telangiectasis, and arteriovenous malformations (AVM) in the brain, lung, liver and gastrointestinal (GI) tract. Although epistaxis is the most common presenting symptom, AVMs affecting the lungs, brain and GI tract provoke a more serious outcome. Heterozygous mutations in endoglin, activin receptor-like kinase 1 (ACVRL1; ALK1), and SMAD4, the genes involved in the transforming growth factor-β family signaling cascade, cause HHT. We report here the case of a 63 year-old male patient who presented melena and GI bleeding episodes, proven to be caused by bleeding from multiple gastric angiodysplasia. Esophagogastroduodenoscopy revealed multiple angiodysplasia throughout the stomach. Endoscopic argon plasma coagulation was performed to control bleeding from a gastric angiodysplasia. The patient has been admitted several times with episodes of hemoptysis and hematochezia. One year ago, the patient was hospitalized due to right-sided weakness, which was caused by left basal ganglia hemorrhage as the part of HHT presentation. In family history, the patients mother and elder sister had died, due to intracranial hemorrhage, and his eldest son has been suffered from recurrent epistaxis for 20 years. A genetic study revealed a mutation in exon 3 of ALK1 (c.199C > T; p.Arg67Trp) in the proband and his eldest son presenting epistaxis.

Acid pump antagonist-provoked HSP27 dephosphorylation and accentuation rescues stomach from indomethacin-induced damages

OBJECTIVE:  Heat shock proteins (HSPs) are crucial for the maintenance of cellular integrity during normal cell growth as well as pathophysiological conditions. While acting as molecular chaperones with their folding activities, HSPs play a cytoprotective role to rescue epithelial cells from several gastric damages including non‐steroidal anti‐inflammatory drugs (NSAIDs) and Helicobacter pylori. Since the exact relationship between HSP27 phosphorylation and biological function remains unknown in NSAID‐induced gastropathy, we hypothesized that revaprazan, a novel acid pump antagonist, can secure significant cytoprotection from NSAID damages through HSP27 accentuation.

Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model.

AIM To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium (DSS)-induced colitis model. METHODS An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin (0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with 50 ng/mL tumor necrosis factor (TNF)-α and then treated with or without rosuvastatin (2 μmol/L). The levels of reactive oxygen species (ROS), inflammatory mediators, and apoptotic markers were measured. RESULTS In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice (P < 0.05). Rosuvastatin also attenuated the DSS-induced increase of 8-hydroxy-2’-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly (ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells (P < 0.05). CONCLUSION Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.

A feasible modified biopsy method for tissue diagnosis of gastric subepithelial tumors.

AIM To evaluate the diagnostic yield and safety of a modified technique for the histological diagnosis of subepithelial tumors (SETs). METHODS A retrospective review of patients who underwent a modified technique for the histological diagnosis of gastric SETs, consisting of a mucosal incision with a fixed flexible snare (MIF) and deep-tissue biopsy under conventional endoscopic view, from January 2012 to January 2013 was performed. Eleven patients with gastric SETs 10-30 mm in diameter and originating from the third or fourth layer on endoscopic ultrasonography were included. RESULTS The mean age was 59.8 (range, 45-76) years, and 5 patients were male. The mean size of the SETs was 21.8 (range, 11-30) mm. The number of biopsy specimens was 6.3 (range 5-8). The mean procedure time was 9.0 min (range, 4-17 min). The diagnostic yield of MIF biopsies was 90.9% (10/11). The histological diagnoses were leiomyoma (4/11, 36.4%), aberrant pancreas (3/11, 27.3%), gastrointestinal stromal tumors (2/11, 18.2%), an inflammatory fibrinoid tumor (1/11, 9.1%); one result was non-diagnostic (1/11, 9.1%). There were six mesenchymal tumors; the specimens obtained in each case were sufficient for an immunohistochemical diagnosis. There was no major bleeding, but one perforation occurred that was successfully controlled by endoscopic clipping. CONCLUSION The MIF biopsy was simple to perform, safe, and required a shorter procedure time, with a high diagnostic yield for small SETs.