Tranilast treatment prevents chronic radiation-induced colitis in rats by inhibiting mast cells infiltration.

INTRODUCTION: Mast cells are the principal cells leading to acute and chronic colitis due to irradiation, radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups: control group (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). The rats in RG and TG were irradiated in the pelvic area (1.5cm from anus) with a single dose of 20 Gray under general anesthesia. Tranilast (100 mg/kg) was intraperitonially injected to mice of the TG for 10 days starting from the day of pelvic irradiation. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were evaluated histologically for the total inflammation score (TIS) and mast cell count. Expression of MUC2, MUC5AC and matrix metalloproteinase 9 (MMP9) were also assessed immunohistochemically. RESULTS: Both TIS and some components of TIS, epithelial atypia, vascular sclerosis and colitis cystica profunda (CCP) were significantly higher in RG than in TG (P=0.02, 0.038, 0.025, 0.01, respectively). The number of infiltrating mast cells was significantly higher in the RG than in TG (20, 3-54 and 6, 3-25, respectively, P=0.034). Quantitatively, the number of MMP9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (P<0.05). TIS and MMP9 exhibited strong associations (correlation coefficient r=0.56, P<0.05) Immunohistochemically, mucin-lake of CCP showed no staining for MUC5AX but positivity for MUC2. CONCLUSION: Tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC in association with the reduction of mast cell infiltration and MMP9 expression.

Colonoscopy decreases mortality in colorectal cancer patients compared with fecal immunochemical test.

BACKGROUND AND AIM: Colonoscopy and fecal immunochemical test (FIT) are commonly used screening methods for the detection of colorectal cancer (CRC), but their effects on survival have not been compared. We compared survival outcomes in patients with CRC according to the exposure history to colonoscopy or FIT before diagnosis of CRC. METHODS: We performed a nationwide population-based retrospective cohort study using Korean national-insurance claims data. In total, 24 875 patients with CRC diagnosed in 2012 were included. The patients were divided into three groups in terms of examinations performed during the 10 years prior to CRC diagnosis: the colonoscopy group, the FIT group, and the never-screened group. Survival outcomes were compared among the three groups. The colonoscopy group and FIT group were matched using propensity score-matching method. RESULTS: The cohort consisted of 9619 patients in the colonoscopy group, 6936 patients in the FIT group, and 8320 patients in the never-screened group. The 5-year overall survival rates were 74.1% in the colonoscopy group, 65.9% in the FIT group, and 59.6% in the never-screened group (P < 0.001). The adjusted hazard ratios for death were 0.56 (95% confidence interval [CI], 0.53-0.59) in the colonoscopy group and 0.78 (95% CI, 0.74-0.82) in the FIT group compared with the never-screened group. In the matched cohort, the adjusted hazard ratios for death was 0.76 (95% CI, 0.72-0.81) in the colonoscopy group compared with the FIT group. CONCLUSION: Colonoscopy is a more effective method for reducing mortality in patients with CRC compared with FIT.

Stool-Based miR-92a and miR-144* as Noninvasive Biomarkers for Colorectal Cancer Screening.

OBJECTIVES: Current noninvasive screening tests for colorectal cancer (CRC) have insufficient sensitivity. MicroRNA (miRNA) levels in stool have potential as markers for noninvasive screening of CRC. We evaluated the diagnostic value of stool miRNA levels and determined the optimal miRNA subtypes for detecting CRC. METHODS: Stool samples were collected from 29 patients with CRC and 29 healthy controls. The stool levels of miR-21, miR-92a, miR-200c, miR-144*, miR-135a, miR-135b, miR-106a, and miR-17-3p were determined by real-time quantitative reverse transcription polymerase chain reaction. The sensitivity and specificity of the miRNAs for CRC were determined by receiver operating characteristics analysis. RESULTS: Among the eight tested miRNAs, the mean stool levels of miR-21, miR-92a, miR-144*, and miR-17-3p differed significantly between the CRC group and the control group (p =0.014, 0.001, <0.001, and 0.008, respectively). The sensitivities and specificities of miR-21, miR-92, miR-144*, and miR-17-3p were 79.3 and 48.3%, 89.7 and 51.7%, 78.6 and 66.7%, and 67.9 and 70.8%, respectively. In a multivariate analysis, miR-92a and miR-144* were significantly associated with the presence of CRC (p = 0.03 and 0.011, respectively). CONCLUSIONS: The stool levels of miR-92a and miR-144* showed good sensitivity and fair specificity for detection of CRC, and thus may be useful as noninvasive biomarkers for this disease.

Diagnostic value of magnetic resonance cholangiopancreatography to detect bile duct stones in acute biliary pancreatitis.

OBJECTIVES: This study aims to evaluate the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) in detecting common bile duct (CBD) stones in acute biliary pancreatitis (ABP). METHODS: The medical records of patients presenting with ABP from January 2008 to July 2013 were reviewed to assess the value of MRCP in detecting CBD stones in ABP. Endoscopic retrograde cholangiopancreatography (ERCP) was used as the reference standard to assess the diagnostic yield of MRCP in detecting choledocholithiasis. When ERCP was unavailable, intraoperative cholangiography or clinical follow-up was used as the reference standard. RESULTS: Seventy-eight patients who underwent MRCP were diagnosed with ABP, and thirty of the 78 patients (38%) were confirmed to have CBD stones per the study protocol. The sensitivity of MRCP in detecting CBD stones in ABP was 93.3% compared to 66.7% for abdominal CT (P < 0.008). The overall accuracy of MRCP in detecting choledocholithiasis was 85.9% compared to 74.0% for abdominal CT (P < 0.041). The area under the receiver operating characteristic curve (AUC) of MRCP in detecting CBD stones was 0.882, which was more accurate than the AUC of 0.727 for abdominal CT (P = 0.039). In 38 patients who underwent ERCP, the sensitivity and negative predictive value of MRCP in detecting CBD stones were both 100% regardless of the dilatation of the bile duct (≥7 mm versus < 7 mm). CONCLUSION: MRCP is an effective, noninvasive modality to detect CBD stones in ABP and can help identify patients who require ERCP.

Clinical outcome of endoscopic management of duodenal Dieulafoy's lesions: endoscopic band ligation versus endoscopic hemoclip placement.

BACKGROUND: The most appropriate type of endoscopic hemostasis for bleeding due to duodenal Dieulafoy's lesions (DLs) is not yet established. The aim of this study was to assess the efficacy of mechanical endoscopic hemostasis for duodenal DLs and long-term outcome after successful hemostasis, as well as to compare the efficacy and safety of endoscopic band ligation (EBL) and endoscopic hemoclip placement (EHP). METHODS: Patients admitted to the emergency unit with acute upper gastrointestinal bleeding from duodenal DLs were enrolled in this study. The data were collected prospectively, but data analysis was performed retrospectively. Twenty-four patients with duodenal DLs were treated with EBL (n = 11) or EHP (n = 13). RESULTS: There were no significant differences between groups with respect to clinical or endoscopic characteristics, apart from the number of epinephrine (three cases with EBL vs. 11 cases with EHP; p = 0.011). Primary hemostasis was achieved in all patients. Recurrent bleeding was observed in one patient (9.1 %) from the EBL group and in five patients (38.5 %) from the EHP group (p = 0.166). The recurrent bleeding in the patient from the EBL group was treated by EHP. In the EHP group, all five patients achieved successful secondary hemostasis by endoscopic treatment (EBL in two patients and EHP in three patients). There were no differences in secondary outcomes between the two groups, including the number of endoscopic sessions required, need for angiographic embolization or emergent surgery, transfusion requirements, or length of hospital stay. No complications occurred, and there was no recurrence of bleeding in either group during the follow-up period. CONCLUSIONS: Mechanical endoscopic treatments are effective and safe for the treatment of bleeding duodenal DLs. A large-scale, randomized, controlled study is required to confirm the efficacy and safety of EBL and EHP for the management of bleeding duodenal DLs.

Circumferential submucosal incision prior to endoscopic mucosal resection provides comparable clinical outcomes to submucosal dissection for well-differentiated neuroendocrine tumors of the rectum.

BACKGROUND: Small rectal neuroendocrine tumors (NETs) can be treated with endoscopic resection. Endoscopic submucosal dissection (ESD) has been accepted as a reliable technique, but it is difficult. We evaluated the feasibility and efficacy of precut and endoscopic mucosal resection (CSI-EMR) for rectal NETs compared to ESD. METHODS: Patients with rectal NETs were enrolled consecutively. ESD or CSI-EMR was performed at operator's discretion. Histological and clinical outcomes were measured and compared between the two treatment modalities. RESULTS: Thirty-three patients were enrolled in the study. Seventeen NETs were treated by the ESD method and 16 were treated by CSI-EMR. Both groups had similar mean tumor diameters (ESD 7.53 ± 1.94 vs. CSI-EMR 6.63 ± 1.99 mm; p = 0.197). En bloc resection was achieved in 100 % of ESD group and 87.5 % of CSI-EMR group. Lateral margin involvement occurred in one patient in ESD group and two in CSI-EMR group. The histologically complete resection rate was 88.2 % (15 of 17) in the ESD group and 81.2 % (13 of 16) in CSI-EMR group (p = 0.592). One case of perforation occurred in both groups. Delayed bleeding did not occur. None of the measured outcomes were different between the two groups. Operating time was significant shorter in CSI-EMR group than in ESD group (9.69 vs. 20.12 min, respectively; p value = 0.004). CONCLUSIONS: CSI-EMR results in reliable clinical outcomes for small rectal NETs comparable to those of ESD. CSI-EMR is technically feasible and more time saving.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

The Effect of Intervention for Improving Colonoscopy Quality Is Associated with the Personality Traits of Endoscopists.

Background/Aims: This study investigated whether the personality traits of endoscopists are associated with the effect of interventions for the improvement of colonoscopy quality. Methods: This prospective, multicenter, single-blind study was performed with 13 endoscopists in three health screening centers over a 12-month period. Quality indicators (QIs), including adenoma detection rate (ADR), polyp detection rate (PDR), and withdrawal time, were measured every 3 months. Consecutive interventions for the improvement of colonoscopy quality were conducted every 3 months, which included the personal notification of QIs, the in-group notification of QIs, and finally a targeted "quality education" session. The personality traits of each endoscopist were evaluated for perfectionism, fear of negative evaluation, and cognitive flexibility after the last QI assessment. Results: A total of 4,095 colonoscopies were evaluated to measure the QIs of the individual endoscopists for 12 months. The mean ADR, PDR, and withdrawal time of the 13 endoscopists were 32.3%, 47.7%, and 394 seconds at baseline and increased to 39.0%, 55.1%, and 430 seconds by the end of the study (p=0.003, p=0.006, and p=0.004, respectively). Among the three interventions, only quality education significantly improved QIs: ADR, 36.0% to 39.0% (odds ratio, 1.28; 95% confidence interval, 1.01 to 1.63). The improvement of ADR and PDR by education was significantly associated with perfectionism (r=0.617, p=0.033 and r=0.635, p=0.027, respectively) and fear of negative evaluation (r=0.704, p=0.011 and r=0.761, p=0.004, respectively). Conclusions: Education can improve colonoscopy quality, and its effect size is associated with an endoscopist's personal traits such as perfectionism and fear of negative evaluation (Clinical-Trials.gov Registry NCT03796169).

A Case of Sporadic Multiple Colonic Polyps in a Young Woman.

Sporadic colorectal cancer arises from an adenoma. As mutations in the adenomatous polyposis coli (APC) tumor suppressor gene have been frequently detected in colorectal adenomas, the APC gene is considered a gatekeeper in colorectal carcinogenesis. Here, we report a case of sporadic multiple colonic adenomas that were accompanied by an APC-truncating mutation. A 25-year-old Korean woman presented with dozens of incidentally found colonic polyps. There was no family history of colorectal polyposis or colon cancer in her first or second-degree relatives. All the polyps were removed endoscopically at once, and their pathological examination revealed tubular adenoma. Mutational analysis showed a 2-bp deletion mutation at codon 443, which generates a premature stop codon at codon 461 of the APC gene, and Western blot analysis demonstrated both wild-type and truncated APC proteins in adenoma tissue. This study suggests that a single truncating mutation of the APC gene may initiate adenoma formation.

In vitro and in vivo phototoxicity on gastric mucosa induced by methylene blue.

Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay. Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. Conclusions: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.

Association between toll-like receptors/CD14 gene polymorphisms and inflammatory bowel disease in Korean population.

The innate immune response in patients who develop inflammatory bowel disease (IBD) may be abnormal. However, the exact role of Toll-like receptors (TLRs) / CD14 gene in the pathogenesis of IBD has not been fully elucidated. We aimed to investigate the association between polymorphisms of TLR1, 2, 4, 6, and CD14 gene and susceptibility to IBD in Korean population. A total 144 patients of IBD (99 patients with ulcerative colitis, 45 patients with Crohn's disease) and 178 healthy controls were enrolled. Using a PCR-RFLP, we evaluated mutations of TLR1 (Arg80Thr), TLR2 (Arg753Gln and Arg677Trp), TLR4 (Asp299Gly and Thr399Ile), TLR6 (Ser249Pro) genes and the -159 C/T promoter polymorphism of CD14 gene. No TLR polymorphisms were detected in Korean subjects. T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls. In subgroup analysis, T allelic frequency was higher in pancolitis phenotype of ulcerative colitis. In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohn's disease.

Simultaneous Integrated Boost Volumetric Modulated Arc Therapy for Rectal Cancer: Long-Term Results after Protocol-Based Treatment.

Background: Volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) is an advanced form of radiotherapy (RT) technology. The purpose of this study was to report long-term treatment outcomes in patients with locally advanced rectal cancer undergoing VMAT-SIB based concurrent chemoradiotherapy (CRT). Methods: Between January 2016 and January 2018, a total of 22 patients with operable stage II-III rectal adenocarcinoma were recruited for the pre-designed VMAT-SIB RT protocol. All patients underwent standard diagnostic and staging work-up. The RT target volumes included the following areas: PTV1 = mesorectum that contained gross tumors and enlarged lymph node regions and PTV2 = mesorectum and regional lymphatics from L4-5/S1 to 3-4 cm below the tumor or levator ani muscle, excluding PTV1. The VMAT-SIB dose prescription was as follows: PTV1 = 52.5 Gy/daily 2.1 Gy/25 fractions, PTV2 = 45 Gy/daily 1.8 Gy/25 fractions. Results: The mean age of the study population was 64 (range, 18-84) years, and 15 (68.2%) patients were male. Radical operation (total mesorectal excision) was performed by either low anterior resection, ultralow anterior resection, or abdominal perineal resection. All five (22.7%) of the patients with confirmed increasing serum carcinoembryonic antigen (CEA) level at diagnosis showed normalization of serum CEA level after the planned treatment. Among 20 patients who underwent preoperative CRT and surgery, tumor down staging in T- and N-stages was achieved in 10 patients (50%) and 13 patients (65%), respectively, with 20% of ypT0/Tis. With a median follow-up of 54.2 (range, 22.6-61.1) months, the 5-year disease-free survival, overall survival, and local control rates were 64.6%, 81.8%, and 84.4%, respectively. Five patients developed distant metastasis and one developed local recurrence as a first event. Two cases with anastomosis site leakage, three with adhesive ileus, and two with abscess formation were observed during postoperative periods. Conclusions: The current VMAT-SIB-based CRT protocol provided acceptable treatment and toxicity outcomes.

Antimigration property of a newly designed covered metal stent for esophageal stricture: an in vivo animal study.

BACKGROUND: Covered self-expandable metal stents (SEMSs) are associated with a higher migration rate than uncovered SEMSs. OBJECTIVE: The antimigration property of a novel covered SEMS was investigated in a canine esophageal stricture model. DESIGN: The new stent (80 mm in length, 20 or 24 mm in diameter) has multiple protuberances on its body that were designed to be separated from the inner silicone membrane so that they could be embedded into the mucosa after deployment. Twenty-two beagle dogs were subjected to circumferential EMR in the middle esophagus for stricture formation. After 2 weeks, conventional covered stents were inserted in a control group (n = 11), and the newly designed covered SEMSs were inserted in a study group (n = 11). SETTING: Animal laboratory. INTERVENTIONS: Circumferential EMR of the middle esophagus for stricture formation, followed by endoscopic placement of a conventional or newly designed stent. MAIN OUTCOME MEASUREMENTS: Migration, complications, survival, and esophageal histopathology. RESULTS: There was no significant difference in the diameter of the esophageal stricture between the control and study groups (10 mm vs 11 mm, P = .52). Within 3 days, all stents in the control group had migrated, whereas 6 had migrated in the study group (100% vs 55%, P = .035). There were no significant complications directly associated with stent insertion. LIMITATIONS: Complications, survival, and esophageal histopathology could not be compared because all of the conventional stents migrated in the control group within 3 days. CONCLUSIONS: The newly designed covered SEMS is more resistant to migration than the conventional covered SEMS.

Differences of urease activity and expression of associated genes according to gastric topography.

BACKGROUND: We hypothesize that pH difference between acid-secreting corpus and non-secreting antrum might influence the activity of H. pylori's urease and/or related genes. We therefore measured urease activity and the expression of amiE whose encoded protein that hydrolyzes short-chain amides to produce ammonia. MATERIALS AND METHODS: Fifty-four patients were recruited into this study. Each gastroscopic biopsy specimen collected from the antrum and body of each patient was immediately used to measure urease activity using serial changes of urease activity (ammonia levels) during 60 minutes. Probe specific for amiE was labeled with a biotin nick-translation kit and was used to detect expression of these genes (mRNA) in fresh-frozen gastroscopic biopsy specimens using fluorescent in situ hybridization (FISH). RESULTS: Urease activity at 60 minutes from the gastric antrum and body of all patients infected with H. pylori was 399.5 ± 490.5 and 837.9 ± 1038.9 µg/dL, respectively (p = .004). Urease activity in the antrum was correlated with H. pylori density. Urease activity or H. pylori density in the antrum was significantly correlated with chronic active inflammation; in contrast, this correlation was not found in the gastric body. The expression level of amiE was 1.5 times higher (p < .05) in the gastric body compared with the antrum. CONCLUSION: Topographically, the urease activity in body was much higher than in antrum. The expression level of amiE was higher in the gastric body compared with the antrum.

A novel technique using endoscopic band ligation for removal of long-stalked (>10 mm) pedunculated colon polyps: A prospective pilot study.

BACKGROUND: Endoscopic removal of large and thick-stalked pedunculated colonic polyps, often leads to massive hemorrhage. Several techniques to minimize this complication have not been widely adopted due to some caveats. In order to prevent postpolypectomy bleeding, we invented a novel technique to dissect long-stalked pedunculated colonic polyps using endoscopic band ligation (EBL) by laterally approaching the stalk. METHODS: In this prospective single-center study, 17 pedunculated polyps in 15 patients were removed between April 2012 and January 2016. We targeted pedunculated polyps with a long stalk length (>10 mm) and a large head (>10 mm) located in the distal colon. After identifying lesions with a colonoscope, we reapproached the middle part of the stalk of the targeted polyp with an EBL-equipped gastroscope to ligate it. Snare polypectomy was performed just above the ligation site of the stalk. RESULTS: EBL-assisted polypectomy removed all of the lesions successfully, which were confirmed pathologically. There was little technical difficulty associated with the endoscopic procedures, regardless of polyp size and stalk thickness, except for one case with a very large polyp that impeded the visualization of the ligation site. We observed a positive correlation between procedure time and the diameter of the head (spearman ρ = 0.52, P = 0.034). After dissection of the polyp, the EBL bands remained fastened to the dissected stalks in all cases. There was no complication associated with polypectomy for 1 month. CONCLUSION: EBL-assisted polypectomy is an easy, safe, and effective technique to remove long-stalked pedunculated colonic polyps without postpolypectomy bleeding.

LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells.

BACKGROUND: As EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It has been reported that viral latent membrane protein 2A (LMP2A) in EBV-transformed tumor cells activates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which provides a survival signal and chemo-resistance to cytotoxic anti-cancer drugs. This study was to evaluate anti-proliferative effect and cell cycle change when 5-FU and LY294002 (LY), a selective inhibitor of PI3K, were treated separately or combined with different schedules in EBV positive gastric cancer cell line, SNU-719. METHODS: After single treatment and sequential combination of 5-FU and LY, cytotoxic activity was measured by MTS assay. When 5-FU and LY were treated in single and sequential combinations, the expression of p-AKT, p-NFkB, p-p53 and bcl-2 was observed on different concentrations by Western blot analysis. We also investigated the effect on apoptosis and cell cycle distribution using flow cytometry. The LMP2A siRNA inhibition was done to confirm the reversal of decreased 5-FU activity and p-AKT. RESULTS: When 5-FU was sequentially combined with LY, the combination index (CI) value indicated synergistic anti-proliferative effect. The expression of p-AKT and p-NF kappaB was upregulated by 5-FU alone but sequential treatment of 5-FU and LY decreased the expression of both p-AKT and p-NF kappaB. When 5-FU was combined with LY, G0/G1 and sub G1 cell population (%) increased. When 5-FU was added to the cells transfected with LMP2A siRNA, its anti-proliferative effect increased and the expression of p-AKT decreased. In sequential combination of 5-FU and LY, the expression of p-p53 was increased and bcl-2 expression was diminished compared to 5-FU alone. CONCLUSION: These data suggest that sequential combination of 5-FU and LY induce synergistic cytotoxicity and overcome intrinsic and acquired resistance of 5-FU via downregulation of activated p-AKT and mitochondria-dependent apoptosis in EBV gastric cancer cell line, SNU-719.

Clinical trial: inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects.

BACKGROUND AND AIM: Revaprazan is a novel acid pump antagonist. The aim of this study was to investigate the inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects. METHODS: In a double-blind, three-way cross-over study, 30 healthy male volunteers were randomized to 100, 150 or 200 mg of oral revaprazan daily for 7 days. Serum gastrin concentration was measured, and 24-h intragastric pH was recorded at baseline and on days 1 and 7 of each administration period. Serial blood samples were processed for pharmacokinetics. RESULTS: Median intragastric pH over 24 h and mean percentage time that pH was > 4 increased in a dose-dependent manner and were significantly higher on days 1 and 7 compared with baseline in all groups (P < 0.05). The antisecretory effect of revaprazan was rapid and nearly maximal on day 1 in all groups. Serum gastrin levels were rapidly normalized by 100 and 150 mg/day of revaprazan on days 1 and 7, but were significantly higher in the 200 mg/day revaprazan group. The pharmacokinetic effect was rapidly absorbed and eliminated on days 1 and 7 in all groups. CONCLUSIONS: Revaprazan rapidly and effectively inhibits gastric acid secretion in healthy male subjects. Therefore, revaprazan can be used as an effective drug for acid-related disease.

Intestinal helminthic infections diagnosed by colonoscopy in a regional hospital during 2001-2008.

The present study investigated characteristics of 24 parasite infection cases detected during colonoscopy in a regional hospital from January 2001 to December 2008. Sixteen patients were confirmed with Trichuris trichiura infection, 6 patients were with Ascaris lumbricoides infection, 1 patient with Enterobius vermicularis infection, and 1 patient with Anisakis infection. Among them, 7 patients (43.8%) were asymptomatic. Colonoscopy findings were normal in 18 patients (75.0%). Among the patients with T. trichiura infection, colonoscopy showed several erosions in 2 patients (8.3%) and non-specific inflammation of the affected segment of the colon in 3 patients (12.5%). In 1 patient with anisakiasis, colonoscopy revealed a markedly swollen colonic wall. Stool examinations were performed before treatment in 7 patients (29.2%) and were all negative for parasite eggs or worms. These results suggest that colonoscopy is a useful diagnostic approach for parasitic infections even for asymptomatic patients and for patients with negative stool examinations.