Influence of Procedural Volume on the Outcome of Gastric Endoscopic Submucosal Dissection: A Nationwide Population-Based Study Using Administrative Data.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a well-established treatment modality for gastric neoplasms. We aimed to investigate the effect of procedural volume on the outcome of ESD for gastric cancer or adenoma. METHODS: In this population-based cohort study, patients who underwent ESD for gastric cancer or adenoma from November 2011 to December 2017 were identified using the Korean National Health Insurance Service database. Operational definitions to identify the target population and post-procedural complications were created using diagnosis and procedure codes and were validated using hospital medical record data. Outcomes included hemorrhage, perforation, pneumonia, 30-day mortality, a composite outcome comprising all of these adverse outcomes, and additional resection. Hospital volume was categorized into 3 groups based on the results of the threshold analysis: high-, medium-, low-volume centers (HVCs, MVCs, and LVCs, respectively). Inverse probability of treatment weighting analysis was applied to enhance comparability across the volume groups. RESULTS: There were 94,246 procedures performed in 88,687 patients during the study period. There were 5886 composite events including 4925 hemorrhage, 447 perforation, and 703 pneumonia cases. There were significant differences in ESD-related adverse outcomes among the 3 hospital volume categories, showing that HVCs and MVCs were associated with a lower risk of a composite outcome than LVCs (inverse probability of treatment-weighted odds ratio [OR], 0.651; 95% CI, 0.521-0.814; inverse probability of treatment-weighted OR, 0.641; 95% CI, 0.534-0.769). Similar tendencies were also shown for hemorrhage, perforation, and pneumonia; however, these were not evident for additional resection. CONCLUSIONS: Procedural volume was closely associated with clinical outcome in patients undergoing ESD for gastric cancer or adenoma.

Developing Operational Definitions Related to Helicobacter pylori Eradication Therapy.

BACKGROUND: The lack of well-established operational definitions is a major limitation of Helicobacter pylori eradication studies that use secondary databases. We aimed to develop and validate operational definitions related to H. pylori eradication therapy. METHODS: Operational definitions were developed by analyzing a nationwide H. pylori eradication registry and validated using real-world data from hospital medical records. The primary endpoint was the sensitivity of the operational definitions in identifying individuals who received H. pylori eradication therapy. The secondary endpoint was the sensitivity and specificity of the operational definition in identifying successful H. pylori eradication therapy. RESULTS: H. pylori eradication therapy was defined as a prescription for one of the following combinations: 1) proton pump inhibitor (PPI) + amoxicillin + clarithromycin, 2) PPI + amoxicillin + metronidazole, 3) PPI + metronidazole + tetracycline, 4) PPI + amoxicillin + levofloxacin, 5) PPI + amoxicillin + moxifloxacin, or 6) PPI + amoxicillin + rifabutin. In the validation set, the sensitivity of the operational definition for identifying individuals who received H. pylori eradication therapy was 99.7% and 99.8% for the first- and second-line therapies, respectively. Operational definition to determine success or failure of the H. pylori eradication therapy was developed based on a confirmatory test and the prescription of rescue therapy. The sensitivity and specificity of the operational definition for predicting successful eradication were 97.6% and 91.4%, respectively, in first-line therapy and 98.6% and 54.8%, respectively, in second-line therapy. CONCLUSION: We developed and validated operational definitions related to H. pylori eradication therapy. These definitions will help researchers perform various H. pylori eradication-related studies using secondary databases.

Clinical Practice Guideline for Gastritis in Korea.

Gastritis is a disease characterized by inflammation of the gastric mucosa. It is very common and has various classification systems such as the updated Sydney system. As there is a lot of evidence that Helicobacter pylori infection is associated with the development of gastric cancer and that gastric cancer can be prevented by eradication, H. pylori gastritis has been emphasized recently. The incidence rate of gastric cancer in Korea is the highest in the world, and due to the spread of screening endoscopy, atrophic gastritis and intestinal metaplasia are commonly diagnosed in the general population. However, there have been no clinical guidelines developed in Korea for these lesions. Therefore, this clinical guideline has been developed by the Korean College of Helicobacter and Upper Gastrointestinal Research for important topics that are frequently encountered in clinical situations related to gastritis. Evidence-based guidelines were developed through systematic review and de novo processes, and eight recommendations were made for eight key questions. This guideline needs to be periodically revised according to the needs of clinical practice or as important evidence about this issue is published in the future.

Multiple functions of pyruvate kinase M2 in various cell types.

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions.

Establishment of Patient-Derived Gastric Cancer Organoid Model From Tissue Obtained by Endoscopic Biopsies.

Cancer organoids are three-dimensional mini-organ analogues derived from cancer tissues and have been proposed as models capable of simulating the structure and function of human organs and tissues in vitro. We sought to establish gastric cancer patient-derived organoids (PDOs) from tissues obtained by endoscopic biopsies. Gastric cancer-PDOs were successfully established and cultured from cancer tissues with gastric adenocarcinoma by endoscopic biopsies. To confirm that gastric cancer-PDOs were derived from cancer tissue, the consistency of the original cancer tissue was assessed by histopathological examination. As a result, it was confirmed that the shape and internal structure of gastric cancer-PDO were derived from the original gastric cancer cells, and the tumor specificity of gastric cancer-PDO was confirmed through Periodic acid-Schiff (PAS) and polyclonal carcinoembryonic antigen antibody staining. These results demonstrate that gastric cancer-PDO models show the characteristics of primary tumors and have potential for drug screening and providing a personalized medicine platform.

Therapeutic Efficacy of a Novel Acetylated Tetrapeptide in Animal Models of Age-Related Macular Degeneration.

It has been shown previously that a novel tetrapeptide, Arg-Leu-Tyr-Glu (RLYE), derived from human plasminogen inhibits vascular endothelial growth factor (VEGF)-induced angiogenesis, suppresses choroidal neovascularization in mice by an inhibition of VEGF receptor-2 (VEGFR-2) specific signaling pathway. In this study, we report that a modified tetrapeptide (Ac-RLYE) showed improved anti-choroidal neovascularization (CNV) efficacy in a number of animal models of neovascular age-related macular degeneration (AMD) which include rat, rabbit, and minipig. The preventive and therapeutic in vivo efficacy of Ac-RLYE via following intravitreal administration was determined to be either similar or superior to that of ranibizumab and aflibercept. Assessment of the intraocular pharmacokinetic and toxicokinetic properties of Ac-RLYE in rabbits demonstrated that it rapidly reached the retina with minimal systemic exposure after a single intravitreal dose, and it did not accumulate in plasma during repetitive dosing (bi-weekly for 14 weeks). Our results suggested that Ac-RLYE has a great potential for an alternative therapeutics for neovascular (wet) AMD. Since the amino acids in human VEGFR-2 targeted by Ac-RLYE are conserved among the animals employed in this study, the therapeutic efficacies of Ac-RLYE evaluated in those animals are predicted to be observed in human patients suffering from retinal degenerative diseases.

P-Tyr42 RhoA GTPase amplifies superoxide formation through p47phox, phosphorylated by ROCK.

Optimal levels of reactive oxygen species (ROS) play a critical role in cellular physiological function. For production of intracellular superoxide, NADPH oxidase is one of the sources. Rac1/2 and RhoA GTPases are involved in regulation of NADPH oxidase activity and Tyr42 phosphorylation of RhoA (p-Tyr42 RhoA) seems significant in this regard as it was recently shown that hydrogen peroxide was able to increase p-Tyr42 RhoA levels. Phorbol myristate acetate (PMA), a tumor promoter, also induces production of superoxides; PMA activates Src, a tyrosine kinase, and increases p-Tyr42 RhoA levels. In exploring the mechanism of PMA effects, we reduced RhoA levels in test cells with si-RhoA and then restoration of various versions of RhoA for effect in response of the cells to PMA and producing superoxides. Restoration of RhoA Y42F (a dephospho-mimic form) still had reduced superoxide formation in response to PMA, compared with WT and Y42E RhoA. This was similarly seen with assays for cell migration and proliferation with cells responding to PMA. Y27632, a ROCK (Rho associated coiled coil kinase) inhibitor, also inhibited superoxide production, and also reduced p-Y416 Src and p-p47phox levels. A ROCK active fragment was also able to phosphorylate p47phox at Ser345 residue (p-Ser345 p47phox), a component of NADPH oxidase. Overall, we demonstrate that p-Tyr42 RhoA levels increase following PMA treatment and this is through production of superoxide and activation of Src. These in turn amplify superoxide production through ROCK phophorylation of p47phox and maintain a positive feedback loop for superoxide generation, and contribute to tumor progression.

Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

Insulin is a critical signaling molecule in reducing blood glucose levels, and pyruvate dehydrogenase (PDH) is an essential enzyme in regulating glucose metabolism. However, the insulin effect on PDH function has not been well established. We observed that insulin attenuated the phosphorylation (p) of Ser264 (p-Ser264) in the PDH E1α subunit (PDHA1) in normal rat hepatocyte. In contrast, insulin induced an increase of p-Ser264 PDHA1 levels in hepatocellular carcinoma HepG2 and Huh7 cells. Insulin activated RhoA and Rho-dependent coiled coil kinase, an effector protein of active RhoA, which regulated p-Ser264 PDHA1 levels, along with both p-Ser9 and p-Tyr216 forms of glycogen synthase kinase-3ß (GSK-3ß) in HepG2 cells. Only p-Tyr216 GSK-3ß, the active form was involved in an increase of p-Ser264 PDHA1. Akt was also engaged in p-Ser9 of GSK-3ß, but neither in p-Tyr216 of GSK-3ß nor p-Ser264 of PDHA1 upon insulin. Reconstituted dephospho-mimic forms PDHA1 S264A and GSK-3ß Y216F impaired, but wild-types PDHA1 and GSK-3ß and phospho-mimic forms PDHA1 S264D and GSK-3ß Y216E increased cell proliferation upon insulin through expression of c-Myc and cyclin D1. Therefore, we propose that insulin-mediated p-PDHA1 is involved in the regulation of HepG2 cell proliferation through RhoA signaling pathway.-Islam, R., Kim, J.-G., Park, Y., Cho, J.-Y., Cap, K.-C., Kho, A.-R., Chung, W.-S., Suh, S.-W., Park, J.-B. Insulin induces phosphorylation of pyruvate dehydrogenase through RhoA activation pathway in HepG2 cells.

The analysis of virulence factors and antibiotic resistance between Helicobacter pylori strains isolated from gastric antrum and body.

BACKGROUND: Individuals can be infected with multiple strains of Helicobacter pylori. However, the differences among co-infecting strains have not been well analyzed yet. This study aimed to investigate whether the virulence factors and antibiotic resistance patterns of H. pylori differ between strains isolated from different locations of the stomach in the same patient. METHODS: H. pylori isolates were obtained from the antrum and body of the stomach. Genetic differences were examined by random amplified polymorphic DNA (RAPD) fingerprinting. Antibiotic resistance was assessed using the agar dilution method. Virulence factors were identified by polymerase chain reaction and DNA sequencing. RESULTS: Among 80 patients, co-infection by two H. pylori strains was detected in 10 patients. Among the 10 pairs of H. pylori strains, differences in antibiotic resistance patterns were detected in 7 pairs (clarithromycin, 1 patient; quinolone, 3 patients; metronidazole, 4 patients) and differences in virulence factors were detected in 5 pairs. The cagA virulence gene was detected in all 10 patients, and 2 patients had H. pylori strains with different EPIYA motifs. Differences in vacA genotypes were detected in 4 patients. CONCLUSIONS: Co-infection by two H. pylori strains was confirmed by RAPD fingerprinting. Frequently, two H. pylori strains obtained from a single host differed in their virulence factors and antibiotic resistance patterns. Co-infection by multiple H. pylori strains could undermine the success of eradication therapy and should be considered when interpreting the results of antimicrobial susceptibility tests.

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.

RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA-RhoGDI complex exists in the cytosol and the active GTP-bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA-GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA-RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c-Myc, HIF-1α/2α, Stat 6, and NF-κB along with several reported microRNAs. As the role of RhoA in regulating actin-filament formation and myosin-actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F-actin)-dependent ("actin switch") or-independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP-1, NF-κB, YAP/TAZ, ß-catenin, and hypoxia inducible factor (HIF)-1α. Interestingly, RhoA also itself is localized to the nucleus by an as-yet-undiscovered mechanism.

The Fatty Liver Index: A Simple and Accurate Predictor of Colorectal Adenoma in an Average-Risk Population.

BACKGROUND: Nonalcoholic fatty liver disease, the hepatic manifestation of metabolic syndrome, is associated with increased risk of colorectal adenoma, a precursor of colorectal cancer. Because nonalcoholic fatty liver disease and colorectal adenoma share many common risk factors of metabolic syndrome, the association between these 2 pathological findings has been investigated in multiple studies, but the results have been conflicting. OBJECTIVE: The present study aimed to assess the relationship between the fatty liver index, a predictor of nonalcoholic fatty liver disease, and the prevalence of colorectal adenomas. DESIGN: This is a retrospective observational study. SETTINGS: This study was conducted at a single expert center. PATIENTS: A total of 2976 consecutive subjects over 40 years of age undergoing routine checkups including abdominal ultrasonography and colonoscopy at Chung-Ang University Hospital Health Care Center were included. MAIN OUTCOME MEASURES: The primary outcome measured was the prevalence of colorectal adenomas according to fatty liver index. RESULTS: Among these subjects, 932 (31.3%) had colorectal adenoma, 691 (23.2%) had metabolic syndrome, and 1512 (50.8%) had fatty liver on ultrasonography. In multivariate analysis, fatty liver index ≥30 was associated with an increased risk of colorectal adenoma (OR, 1.269; 95% CI, 1.06-1.49; p = 0.008). The fatty liver index-high group (fatty liver index ≥30) had more colorectal adenomas and more advanced colorectal adenomas than the fatty liver index-low group (fatty liver index <30) (p < 0.001 and p = 0.042). The prevalence of colorectal adenomas increased with increasing quartile of fatty liver index (p < 0.05). LIMITATIONS: The study was limited by a relatively healthy Asian population. CONCLUSION: The high fatty liver index may be a useful predictor of colorectal adenoma. See Video Abstract at http://links.lww.com/DCR/A478.

Wnt3A Induces GSK-3ß Phosphorylation and ß-Catenin Accumulation Through RhoA/ROCK.

In canonical pathway, Wnt3A has been known to stabilize ß-catenin through the dissociation between ß-catenin and glycogen synthase kinase-3ß (GSK-3ß) that suppresses the phosphorylation and degradation of ß-catenin. In non-canonical signaling pathway, Wnt was known to activate Rho GTPases and to induce cell migration. The cross-talk between canonical and non-canonical pathways by Wnt signaling; however, has not been fully elucidated. Here, we revealed that Wnt3A induces not only the phosphorylation of GSK-3ß and accumulation of ß-catenin but also RhoA activation in RAW264.7 and HEK293 cells. Notably, sh-RhoA and Tat-C3 abolished both the phosphorylation of GSK-3ß and accumulation of ß-catenin. Y27632, an inhibitor of Rho-associated coiled coil kinase (ROCK) and si-ROCK inhibited both GSK-3ß phosphorylation and ß-catenin accumulation. Furthermore, active domain of ROCK directly phosphorylated the purified recombinant GSK-3ß in vitro. In addition, Wnt3A-induced cell proliferation and migration, which were inhibited by Tat-C3 and Y27632. Taken together, we propose the cross-talk between canonical and non-canonical signaling pathways of Wnt3A, which induces GSK-3ß phosphorylation and ß-catenin accumulation through RhoA and ROCK activation. J. Cell. Physiol. 232: 1104-1113, 2017. © 2016 Wiley Periodicals, Inc.

Abdominal Visceral to Subcutaneous Adipose Tissue Ratio Is Associated with Increased Risk of Erosive Esophagitis.

BACKGROUND: To investigate the association between abdominal fat distribution represented by the visceral fat area (VFA) to subcutaneous fat area (SFA) ratio, and erosive esophagitis (EE). METHODS: Seven hundred and twenty-eight participants aged >40 years underwent physical examination, blood tests, esophagogastroduodenoscopy, and abdominal computer tomography at Chung-Ang University Hospital from 2007 to 2012. RESULTS: Of 728 subjects, 65 (8.9%) had EE. The EE patients had higher body mass index, metabolic syndrome prevalence, triglyceride levels, and blood pressure (P < 0.05). The mean VFA/SFA ratio was higher in the EE group than in the non-EE group (1.30 vs. 0.92, P < 0.001). The predominance of EE in the group with higher VFA/SFA ratio was higher than in the group with lower VFA/SFA ratio (P < 0.001). A VFA/SFA ratio ≥1.165 had good accuracy to predict EE (area under the receiver-operating characteristic curve, 0.643). The VFA/SFA ratio and visceral fat volume were positively correlated with the severity of EE (P = 0.002), and a VFA/SFA ratio ≥1.165 was strongly correlated with the severity of EE (P < 0.001). CONCLUSION: The high VFA/SFA ratio can be a useful clinical predictor of EE.

Eradication Rates of Helicobacter pylori in Korea Over the Past 10 years and Correlation of the Amount of Antibiotics Use: Nationwide Survey.

BACKGROUND: The efficacy of proton-pump inhibitor-amoxicillin-clarithromycin therapy for H. pylori eradication has decreased over time. OBJECTIVE: We assessed the trend of H. pylori eradication rates over the last 10 years and the relationship between the eradication rates and the amount of macrolide antibiotic use in a country with a high prevalence of H. pylori infection. METHODS: This vast nationwide multicenter study was conducted with 34,139 adults treated for H. pylori infection from January 2001 to December 2010. The defined daily dose per km(2) (DSD) of macrolide antibiotics was calculated (n = 141,019) using the Health Insurance Review & Assessment data base from 2008 to 2010 in the two cities which had the lowest (Jeju city) or highest (Chuncheon city) eradication rate. RESULTS: The eradication rates of proton-pump inhibitor-amoxicillin-clarithromycin therapy ranged 84.9-87.5% from 2001 to 2007, and those of 2008 to 2010 ranged 80.0-81.4% with a decreasing trend (p < 0.0001). The decreasing trend of eradication rates for the overall first-line therapy was observed only in three of the seven geographic areas in Korea (p < 0.0001). The DSD of macrolide antibiotics was significantly higher in Jeju than Cheunchon city (0.85 vs 0.52, p < 0.0001). CONCLUSIONS: H. pylori eradication rates with clarithromycin-containing triple therapy in Korea showed a decreasing trend over the past 10 years, although the trend varied among geographic areas. This difference may be associated with the amount of macrolide antibiotic use.

IκB kinase γ/nuclear factor-κB-essential modulator (IKKγ/NEMO) facilitates RhoA GTPase activation, which, in turn, activates Rho-associated KINASE (ROCK) to phosphorylate IKKß in response to transforming growth factor (TGF)-ß1.

Transforming growth factor (TGF)-ß1 plays several roles in a variety of cellular functions. TGF-ß1 transmits its signal through Smad transcription factor-dependent and -independent pathways. It was reported that TGF-ß1 activates NF-κB and RhoA, and RhoA activates NF-κB in several kinds of cells in a Smad-independent pathway. However, the activation molecular mechanism of NF-κB by RhoA upon TGF-ß1 has not been clearly elucidated. We observed that RhoA-GTP level was increased by TGF-ß1 in RAW264.7 cells. RhoA-GDP and RhoGDI were bound to N- and C-terminal domains of IKKγ, respectively. Purified IKKγ facilitated GTP binding to RhoA complexed with RhoGDI. Furthermore, Dbs, a guanine nucletotide exchange factor of RhoA much more enhanced GTP binding to RhoA complexed with RhoGDI in the presence of IKKγ. Indeed, si-IKKγ abolished RhoA activation in response to TGF-ß1 in cells. However, TGF-ß1 stimulated the release of RhoA-GTP from IKKγ and Rho-associated kinase (ROCK), an active RhoA effector protein, directly phosphorylated IKKß in vitro, whereas TGF-ß1-activated kinase 1 activated RhoA upon TGF-ß1 stimulation. Taken together, our data indicate that IKKγ facilitates RhoA activation via a guanine nucletotide exchange factor, which in turn activates ROCK to phosphorylate IKKß, leading to NF-κB activation that induced the chemokine expression and cell migration upon TGF-ß1.

Efficacy of Lafutidine Versus Famotidine in Patients with Reflux Esophagitis: A Multi-Center, Randomized, Double-Blind, Non-inferiority Phase III Trial.

BACKGROUND: There has been no study on the efficacy of lafutidine for patients with reflux esophagitis in Korea. AIM: To evaluate the efficacy of a new-generation histamine-2 receptor antagonist, lafutidine, in comparison with famotidine in patients with reflux esophagitis. METHODS: This was a randomized, double-blind, non-inferiority trial enrolling patients with erosive esophagitis. The efficacy and safety of 20 mg lafutidine (treatment group) were compared with those of 40 mg famotidine (control group) and 20 mg omeprazole (reference group). The primary endpoint was the complete healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment. The non-inferiority margin was assumed to be -15 %. RESULTS: The healing rates of reflux esophagitis on endoscopy after 8 weeks of treatment were 70.14 % (101/144) in the lafutidine, 63.45 % (92/145) in the famotidine, and 85.71 % (126/147) in the omeprazole group. The difference in healing rates between the lafutidine and famotidine groups was 6.69 % (95 % confidence interval = [-4.14 to 17.52]). In addition, lafutidine was superior to famotidine in clinical improvement (53.73 % vs. 39.55 %, P = 0.0200). CONCLUSIONS: Lafutidine was non-inferior to famotidine in healing of reflux esophagitis. Lafutidine, however, was superior to famotidine in terms of symptom relief of reflux esophagitis.

Treatment of Helicobacter pylori Infection in Korea: A Systematic Review and Meta-analysis.

The efficacy of seven-day clarithromycin-based standard triple therapy (STT) for Helicobacter pylori has decreased in Korea over the past decade. The aim of this meta-analysis was to clarify the efficacy of first-line and second-line therapies in Korea. This systematic review will provide an overview of H. pylori eradication and present new therapeutic strategies used in Korea. An extensive search of the literature concerning STT, sequential therapy (SET), concomitant therapy (CT), bismuth-containing quadruple therapy (BCQT) and various other therapies used in Korea was performed. All selected studies were randomized controlled trials (RCTs). Eighteen RCTs were eligible for systematic review. The alternative regimens comparing seven-day STT as a first-line therapy include SET, CT, levofloxacin-based therapy (LBT), BCQT, and STT with prolonged duration. The results of the meta-analysis suggest that SET is superior to seven-day STT. The overall eradication rate by intention to treat (ITT) analysis was 69.8% for STT and 79.7% for SET. The overall eradication rate by per-protocol (PP) analysis was 77.0% for STT and 85.0% for SET. The odds ratios for the ITT and PP eradication rate were 0.57 (95% confidence interval [CI], 0.43 to 0.74) and 0.52 (95% CI, 0.35 to 0.76), respectively. In the subgroup analysis, however, there were no significant differences between SET and STT with prolonged durations. Alternative regimens to seven-day BCQT as second-line therapy include LBT, moxifloxacin-based therapy and 14-day BCQT. The eradication rates of these alternative regimens were not superior to that of the conventional treatment. SET is superior to seven-day STT but not to STT with prolonged duration.

Comparison of the efficacy of 4- and 8-week lansoprazole treatment for ESD-induced gastric ulcers: a randomized, prospective, controlled study.

BACKGROUND: Although endoscopic submucosal dissection (ESD) is widely used to treat gastric neoplasms, there is no consensus for the optimal treatment for ESD-induced ulcers. We compared efficacy between 4 and 8 weeks of lansoprazole treatment for iatrogenic gastric ulcers that developed after ESD. METHODS: Eighty-four patients who were diagnosed with gastric adenoma or early gastric cancer were enrolled and randomly assigned to treatment with lansoprazole (30 mg/day) for 4 or 8 weeks. Eight weeks after ESD, we conducted follow-up endoscopy to compare ulcer stage and ulcer reduction ratio (dividing the ulcer dimension at 8 weeks by the initial ulcer dimension) between the two groups. RESULTS: From the 84 patients, 69 patients were included in the final analysis, with 34 in the 4-week group and 35 in the 8-week group. Eight weeks after ESD, there were no significant difference observed between the two groups in terms of the ulcer stage (68 % in the scar stage in the 4-week group vs. 69 % in the 8-week group, P = 0.93) or the ulcer reduction ratio (0.0081 ± 0.015 in the 4-week group vs. 0.0037 ± 0.008 in the 8-week group, P = 0.15). Also, in the subgroup analysis among the patients with large ulcers (>30 mm), those parameters were not different. CONCLUSIONS: For ESD-induced gastric ulcers, treatment with lansoprazole for 4 weeks was as effective as treatment for 8 weeks. Considering cost-effectiveness, proton pump inhibitor therapy for 4 weeks may be sufficient for ESD-induced gastric ulcers.

Clarithromycin-based standard triple therapy can still be effective for Helicobacter pylori eradication in some parts of the Korea.

We evaluated the antibiotic resistance rates and eradication rates of clarithromycin based triple therapy from 2005 to 2010 retrospectively. In addition, we investigated the mechanism of clarithromycin resistance in Helicobacter pylori strains isolated from Korean patients. Two hundred and twelve strains of H. pylori were isolated from 204 patients. H. pylori ATCC 43504 was used as the standard strain. The eradication rates of H. pylori from 2005 to 2010 were 89.3%, 82.6%, 86.3%, 87.7%, 81.8%, and 84.2%, respectively. Total eradication rate was 84.9%. DNA sequences of the 23S RNA gene in clarithromycin-resistant strains were determined. The resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, moxifloxacin, and levofloxacin were 9.0%, 8.5%, 36.3%, 0%, 14.2%, 14.2%, and 14.2%, respectively. The multidrug resistance rate of H. pylori was 16.5%. Sequence analysis of clarithromycin-resistant strains showed an A2144G mutation in 8 of 14 strains (57.1%), a T2183C mutation in 5 of 14 strains (35.7%), and double mutations of both A2144G and T2183C in 1 of 14 strains (7.1%). In the present study, triple therapy may still be an effective eradication therapy for H. pylori infections in Korea. The A2144G and T2183C mutations are mainly present in clarithromycin-resistant isolates.

Increasing correlation between oral and gastric microbiota during gastric carcinogenesis.

Background/Aims: Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes. Methods: We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis. Results: We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems). Conclusions: During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.