DNA mismatch repair deficiency and outcomes of patients with locally advanced gastric cancer treated with preoperative docetaxel, oxaliplatin, and S-1 plus surgery and postoperative S-1 or surgery plus postoperative S-1: a sub-analysis of the phase 3 PRODIGY trial.

BACKGROUND: The benefit of adjuvant chemotherapy for locally advanced gastric cancer (LAGC) patients with DNA mismatch repair (MMR) deficiency (D-MMR) is controversial due to concerns about its potential detrimental effect. The PRODIGY trial showed the survival benefit of adding preoperative docetaxel, oxaliplatin, and S-1 (DOS) to surgery plus postoperative S-1 for LAGC patients. In this sub-analysis, we evaluated the benefit of preoperative DOS according to MMR status. METHODS: Among patients enrolled in the PRODIGY trial treated with either preoperative DOS followed by surgery and postoperative S-1 (CSC arm), or surgery and postoperative S-1 (SC arm) at Asan Medical Center (n = 249), those in the full analysis set with available tissue to assess MMR status were included in the present analysis. RESULTS: A total of 231 patients (CSC arm, n = 108; SC arm, n = 123) were included (median age, 58 years [range, 27-75]), and 21 patients (CSC arm, n = 8 [7.4%]; SC arm, n = 13 [10.6%]) had D-MMR tumors. Progression-free survival and overall survival tended to be superior in the CSC arm than in the SC arm among D-MMR patients (HR 0.48 [95% CI 0.09-2.50]; log-rank P = 0.37 and HR 0.55 [95% CI 0.11-2.86]; log-rank P = 0.46, respectively), as well as among proficient MMR (P-MMR) patients (HR 0.68 [95% CI 0.46-1.03]; log-rank P = 0.07 and HR 0.75 [95% CI 0.49-1.14]; log-rank P = 0.17, respectively). CONCLUSION: Preoperative DOS followed by surgery and postoperative S-1 may be considered a treatment option for LAGC patients regardless of MMR status.

Local administration of shikonin improved the overall survival in orthotopic murine glioblastoma models with temozolomide resistance.

BACKGROUND: Glioblastoma is a type of intracranial malignancy. Shikonin, a Chinese traditional medicine, has been shown to have anti-tumor efficacy toward human glioblastoma cells in vitro. However, shikonin cannot easily cross the blood-brain barrier. To address this issue, we evaluated the anti-tumor effects of direct intracranial infusion of shikonin in in vivo orthotopic syngeneic murine glioblastoma models using C57BL/6 mice. MATERIALS AND METHODS: The cytotoxic effects of shikonin against murine glioblastoma cells, SB28 and CT-2A, were reported resistance to temozolomide, were evaluated using an allophycocyanin-conjugated annexin V and propidium iodide assay with flow cytometry. Impedance-based real-time cell analysis (RTCA) was used to analyze the inhibitory effects of shikonin on growth and proliferation. To evaluate the anti-tumor activity of shikonin in vivo, we used orthotopic syngeneic murine glioblastoma models with SB28 and CT-2A cells. RESULTS: In flow cytometry-based cytotoxic assays, shikonin induced apoptosis. RTCA indicated that shikonin decreased the cell index of murine glioblastoma cells, SB28 and CT-2A, in a dose-dependent manner (p < 0.0001 for both cell lines), while temozolomide did not (p = 0.91 and 0.82, respectively). In murine glioblastoma models, SB28 and CT-2A, direct intracranial infusion of shikonin, as a local chemotherapy, improved the overall survival of mice in a dose-dependent manner compared with control groups (p < 0.0001 and p = 0.02, respectively). While temozolomide did not (p = 0.48 and 0.52, respectively). CONCLUSIONS: The direct intracranial infusion of shikonin has potential as a local therapy for patients with glioblastoma.

Comparative and expression analyses of AP2/ERF genes reveal copy number expansion and potential functions of ERF genes in Solanaceae.

BACKGROUND: The AP2/ERF gene family is a superfamily of transcription factors that are important in the response of plants to abiotic stress and development. However, comprehensive research of the AP2/ERF genes in the Solanaceae family is lacking. RESULTS: Here, we updated the annotation of AP2/ERF genes in the genomes of eight Solanaceae species, as well as Arabidopsis thaliana and Oryza sativa. We identified 2,195 AP2/ERF genes, of which 368 (17%) were newly identified. Based on phylogenetic analyses, we observed expansion of the copy number of these genes, especially those belonging to specific Ethylene-Responsive Factor (ERF) subgroups of the Solanaceae. From the results of chromosomal location and synteny analyses, we identified that the AP2/ERF genes of the pepper (Capsicum annuum), the tomato (Solanum lycopersicum), and the potato (Solanum tuberosum) belonging to ERF subgroups form a tandem array and most of them are species-specific without orthologs in other species, which has led to differentiation of AP2/ERF gene repertory among Solanaceae. We suggest that these genes mainly emerged through recent gene duplication after the divergence of these species. Transcriptome analyses showed that the genes have a putative function in the response of the pepper and tomato to abiotic stress, especially those in ERF subgroups. CONCLUSIONS: Our findings will provide comprehensive information on AP2/ERF genes and insights into the structural, evolutionary, and functional understanding of the role of these genes in the Solanaceae.

[A Randomized, Double-blind, Active-controlled Exploratory Clinical Trial for the Evaluation of the Efficacy and Safety of Goodmorning S Granule® on Constipation].

Background/Aims: Constipation is a common gastrointestinal disease that reduces the quality of life and incurs considerable medical expenses. Bisacodyl and sodium docusate are generally used to treat constipation. This study assessed the effectiveness and safety of Goodmorning S Granule® (Hanpoong Pharm. Co., Ltd., Wanju, Korea) in functional constipation by a comparison with bisacodyl. Methods: A 2-week randomized, double-blind, active-controlled exploratory clinical trial was conducted to compare the treatment (Goodmorning S Granule®) with the control (bisacodyl). The efficacy was measured by the changes in transition, Bristol stool type, stomachache, clinical manifestation, defecation time after drug consumption, 36-item short-form survey (SF-36), and the results of improvement evaluation. The safety was evaluated by the incidence of adverse drug events and vital signs. Additional analyses were conducted by dividing the severity according to the proportion of Bristol Stool Scale types 1 and 2. Results: Subjects were randomized to the treatment (n=24) or control (n=26) groups. No significant differences were observed in demographics. After 2 weeks from the baseline, the changes in the complete spontaneous bowel movement (CSBM) were higher in the treatment (4.00±2.62) group than in the control group (1.40±2.34) (p<0.05). The treatment group exhibited significant improvement in the score on the SF-36 questionnaire. The clinical side effects, such as stomachache and borborygmus, were reduced in the moderate constipation patients in the treatment group, according to additional analyses. Conclusions: Goodmorning S Granule®, a herbal medicine, was more effective in improving quality of life and CSBM per week and safer in the moderate constipation groups because of the reduced clinical side effects.

Efficacy of DA-5204 (Stillen 2X) for patients with gastroesophageal reflux disease: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND/AIM: Proton pump inhibitor (PPI) alone is not satisfactory for the treatment of gastroesophageal reflux disease (GERD). Therefore, we investigated the efficacy of DA-5204 (Stillen 2X, 90 mg of Artemisia asiatica 95% ethanol extract per tablet) and PPI combination therapy on GERD in comparison to PPI alone. METHODS: This randomized, double-blind, placebo-controlled study randomly assigned 70 patients with endoscopically proven esophageal mucosal injury (Los Angeles classification grade A or B) into 2 groups: pantoprazole 40 mg once daily with DA-5204 twice daily (DA-5204 group) or pantoprazole 40 mg once daily with placebo twice daily (placebo group) for 4 weeks. The primary endpoint was endoscopic healing rate. The secondary endpoint was sufficient relief (≥50% reduction) of symptoms using GERD Questionnaire. RESULTS: Final analyses included 29 patients with the DA-5204 group and 30 patients with the placebo group. At weeks 4, there was no significant difference in the endoscopic healing rate between the 2 groups (DA-5204 vs placebo; 96.6% vs 93.3%; P = 1.000). However, the rate of residual minimal change was significantly lower in the DA-5204 group (5/28, 17.9%) than in the placebo group (17/28, 60.7%) (P < .001). The rates of symptom relief were not different between the DA-5204 group and the placebo group (all P > .05). CONCLUSION: Combined therapy with PPI and DA-5204 has no additional effect on the endoscopic healing rate compared to PPI alone. However, it may be beneficial in resolving minimal change.

Annual eradication rate of bismuth-containing quadruple therapy as second-line treatment for Helicobacter pylori infection: A 15-year prospective study at a tertiary hospital in Korea.

BACKGROUND: Bismuth-containing quadruple therapy is widely used as second-line treatment for Helicobacter pylori infection. This prospective study investigated the changes in the annual H. pylori eradication rates of quadruple therapy. METHODS: This study included an intention-to-treat (ITT) population of 452 subjects who failed first-line eradication therapy for H. pylori between 2003 and 2018. All subjects received a 14-day course of bismuth-containing quadruple therapy consisting of esomeprazole (40 mg twice daily), metronidazole (500 mg thrice daily), bismuth subcitrate (120 mg four times daily), and tetracycline (500 mg four times daily). Per-protocol (PP) analysis of data was performed in subjects who followed up with strict treatment adherence. Eradication was confirmed based on the results of the 13 C-urea breath test, rapid urease test (CLOtest® ), and histopathologic evaluation. Compliance and adverse effects were also investigated. A minimal inhibitory concentration test was performed on tissue samples obtained from 103 subjects. RESULTS: The overall eradication rates following ITT and PP analyses were 78.8% (356/452) and 89.5% (314/351), respectively. The annual eradication success rate did not show significant changes (P = .062 [ITT], P = .857 [PP]) over the 15-year study period. Adverse events were reported in 57.3% of the ITT population. The rates of resistance to metronidazole and tetracycline were 44.7% and 18.4%, respectively. CONCLUSIONS: Despite high antibiotic resistance rates, no significant reduction in annual eradication rates was observed during the study period.

[Inhibitory Effects of ß-caryophyllene on Helicobacter pylori Infection: A Randomized Double-blind, Placebo-controlled Study].

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infections, which cause a variety of gastrointestinal symptoms, are common in South Korea. Recent reports have shown a decline in the H. pylori eradication rates. ß-caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species, such as cloves, basil, and cinnamon. ß-caryophyllene has been reported to have anti-inflammatory and anti-bacterial effects. This study investigated the inhibitory effects of ß-caryophyllene on H. pylori and its potential role as an alternative gastrointestinal drug. METHODS: This 8-week, randomized double-blind, placebo-controlled trial categorized subjects into a ß-caryophyllene group (33 patients who received 126 mg/day of ß-caryophyllene) and a placebo group (33 patients who received a placebo preparation). The inflammation level of H. pylori infiltration and the eradication rates were evaluated endoscopically and with the urea breath test (UBT) in both groups before and after administering the medication. The serum cytokine levels (tumor necrosis factor-α, and interleukin [IL]-1ß and IL-6) were compared in both groups before and after administering the medication. RESULTS: Complete eradication was not observed in either group. Moreover, there was no significant change in the UBT and updated Sydney score. On the other hand, the ß-caryophyllene group showed significant improvement in nausea (p=0.025) and epigastric pain (p=0.018), as well as a decrease in the serum IL-1ß levels (p=0.038). CONCLUSIONS: ß-caryophyllene improves dyspepsia symptoms and can be considered a useful supplementary treatment for gastrointestinal disease.

Effects of Alkaline-Reduced Drinking Water on Irritable Bowel Syndrome with Diarrhea: A Randomized Double-Blind, Placebo-Controlled Pilot Study.

OBJECTIVES: The purpose of this study was to investigate whether the ingestion of alkaline-reduced water (ARW) is helpful in improving the symptoms of diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Twenty-seven patients (male, 25.9%; mean, 41.7 years old) with diarrhea-predominant IBS were randomly allocated to two groups. For eight weeks, the ARW group (n = 13) ingested at least 2 liters/day of ARW, while the control group (n = 14) ingested placebo water. IBS symptom scores (quality-of-life, abdominal pain/discomfort), stool form, and frequency were assessed before and after treatment via questionnaires. RESULTS: Eight patients (61.5%) in the ARW group and six patients (42.9%) in the control group indicated that their symptoms had improved in more than four out of the eight weeks of treatment (p = 0.449). The IBS quality-of-life score significantly improved from 57.2 to 30.8 in the ARW group; this improvement was significantly greater than the slight improvement from 48.7 to 42.2 observed in the control group (p = 0.029). The abdominal pain score improved from 1.8 to 0.9 in the ARW group and from 1.8 to 1.1 in the control group, with no significant group difference (p = 0.232). CONCLUSIONS: Drinking ARW for eight weeks improves the quality of life in patients with diarrhea-predominant IBS.

[The Efficacy of Bismuth-containing Quadruple Therapy after Moxifloxacin-based Sequential Therapy Failure in Helicobacter pylori Eradication].

Background/Aims: Moxifloxacin-based sequential therapy showed an excellent eradication rate as the first line treatment of Helicobacter pylori (H. pylori) infection. However, to the best of our knowledge, there were only a few studies on the treatment of those with failed moxifloxacin-based sequential therapy. Hence, this study was to investigate the efficacy of bismuth-containing quadruple therapy in those with failed moxifloxacin-based sequential or reverse sequential therapy for H. pylori eradication. Methods: Between January 2013 and March 2016, we retrospectively analyzed patients who failed to eradicate H. pylori using moxifloxacin-based sequential (rabeprazole 20 mg bid and amoxicillin 1 g bid for 5-7 days, followed by rabeprazole 20 mg bid, metronidazole 500 mg bid, and moxifloxacin 400 mg qd for 5-7 days) and 10 days moxifloxacin-based reverse sequential therapy as the first line treatment. Then we investigated the eradication rates of bismuth-containing quadruple therapy as the second line treatment. All subjects had no history of H. pylori eradication before. Eradication rates were described as intention-to-treat (ITT) and per-protocol (PP) analyses. H. pylori status was evaluated by ¹³C-urea breath test 6 weeks after the end of the treatment. Moreover, we examined any side effects that caused discontinuation of therapy. Results: Twenty-three patients received bismuth-containing quadruple therapy as the second line treatment. The overall eradication rates by ITT and PP analyses were 60.87% (n=14/23) and 73.68% (n=14/19). All the patients showed good compliance, and there were no serious adverse events. Conclusions: Bismuth-containing quadruple therapy is insufficient as the second line eradication treatment after a failed attempt of moxifloxacin-based sequential or reverse sequential therapy. Large-scale clinical trials should be performed to establish better clinical evidence.

Green tea extracts for the prevention of metachronous colorectal polyps among patients who underwent endoscopic removal of colorectal adenomas: A randomized clinical trial.

OBJECTIVES: To determine the preventive effect of green tea extract (GTE) supplements on metachronous colorectal adenoma and cancer in the Korean population. MATERIALS AND METHODS: One hundred seventy-six subjects (88 per each group) who had undergone complete removal of colorectal adenomas by endoscopic polypectomy were enrolled. They were randomized into 2 groups: supplementation group (0.9 g GTE per day for 12 months) or control group without GTE supplementation. The 72-h recall method was used to collect data on food items consumed by participants at baseline and the 1-year follow-up during the past 48 h. Follow-up colonoscopy was conducted 12 months later in 143 patients (71 in control group and 72 in the GTE group). RESULTS: Of the 143 patients completed in the study, the incidences of metachronous adenomas at the end-point colonoscopy were 42.3% (30 of 71) in control group and 23.6% (17 of 72) in GTE group (relative risk [RR], 0.56; 95% confidence interval [CI], 0.34-0.92). The number of relapsed adenoma was also decreased in the GTE group than in the control group (0.7 ± 1.1 vs. 0.3 ± 0.6, p = 0.010). However, there were no significant differences between the 2 groups in terms of body mass index, dietary intakes, serum lipid profiles, fasting serum glucose, and serum C-reactive protein levels (all p > 0.05). CONCLUSION: This study of GTE supplement suggests a favorable outcome for the chemoprevention of metachronous colorectal adenomas in Korean patients (ClinicalTrials.gov number, NCT02321969).

[The Efficacy of Moxifloxacin-containing Triple Therapy after Hybrid Therapy Failure in Helicobacter pylori Eradication].

BACKGROUND/AIMS: Hybrid therapy was successful in eradicating Helicobacter pylori (H. pylori) according to previous reports. However, to the best of our knowledge, there have only been a few studies evaluating the optimal choice after hybrid failure. Hence, we aimed to evaluate the efficacy of moxifloxacin-containing triple therapy after hybrid therapy failure in H. pylori eradication. METHODS: Between January 2013 and March 2016, we retrospectively reviewed patients who underwent failed hybrid therapy, as first line treatment, in eradicating H. pylori (rabeprazole and amoxicillin b.i.d for 14 days, in addition to clarithromycin and metronidazole b.i.d for final 7 days). Then, we investigated the eradication rates of moxifloxacin-containing triple therapy (rabeprazole, amoxicillin b.i.d and moxifloxacin qd) as the second line of treatment. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to determine the eradication rate. We evaluated the status of H. pylori by using 13C-urea breath test 6 weeks after the final treatment. Moreover, compliance and adverse effects of each patient were analyzed. RESULTS: Among those who failed the initial hybrid therapy, 11 patients received moxifloxacin-containing triple therapy. The overall eradication rates, as determined by ITT and PP, were 72.7% (n=8/11) and 80% (n=8/10), respectively. The compliance rate was 100%, and there were no serious adverse effects. CONCLUSIONS: Moxifloxacin-containing triple therapy can be used as a second line therapy in case of hybrid therapy failure. A large scale study is necessary to confirm the findings of this study and establish clinical evidence.

Risk Factors for Vitamin D, Zinc, and Selenium Deficiencies in Korean Patients with Inflammatory Bowel Disease.

BACKGROUND/AIMS: Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD. METHODS: We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls. RESULTS: Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; p<0.001). The proportions of patients with lower serum zinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn's disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (<3.3 g/dL) (p=0.047) were risk factors for selenium deficiency. CONCLUSIONS: Many Korean patients with IBD have vitamin D, zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients.

Effects of N-acetylcysteine on First-Line Sequential Therapy for Helicobacter pylori Infection: A Randomized Controlled Pilot Trial.

BACKGROUND/AIMS: To evaluate the adjuvant effects of N-acetylcysteine (NAC) on first-line sequential therapy (SQT) for Helicobacter pylori infection. METHODS: Patients with H. pylori infections were randomly assigned to receive sequential therapy with (SQT+NAC group, n=49) or without (SQT-only group, n=50) NAC. Sequential therapy consisted of rabeprazole 20 mg and amoxicillin 1 g for the first 5 days, followed by rabeprazole 20 mg, clarithromycin 500 mg and metronidazole 500 mg for the remaining 5 days; all drugs were administered twice daily. For the SQT+NAC group, NAC 400 mg bid was added for the first 5 days of sequential therapy. H. pylori eradication was evaluated 4 weeks after the completion of therapy. RESULTS: The eradication rates by intention-to-treat analysis were 58.0% in the SQT-only group and 67.3% in the SQT+NAC group (p=0.336). The eradication rates by per-protocol analysis were 70.0% in the SQT-only group and 80.5% in the SQT+NAC group (p=0.274). Compliance was very good in both groups (SQT only/SQT+NAC groups: 95.2%/100%, p=0.494). There was no significant difference in the adverse event rates between groups (SQT-only/SQT+NAC groups: 26.2%/26.8%, p=0.947). CONCLUSIONS: The H. pylorieradication rate was numerically higher in the SQT+NAC group than in the SQT-only group. As our data did not reach statistical significance, larger trials are warranted.

Moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori infection.

AIM: To assess the efficacy of moxifloxacin-containing triple therapy after non-bismuth quadruple therapy failure for Helicobacter pylori (H. pylori) eradication. METHODS: Between January 2010 and December 2012, we screened individuals who were prescribed non-bismuth quadruple therapy for H. pylori eradication. Among them, a total of 98 patients who failed non-bismuth quadruple therapy received 1-wk or 2-wk moxifloxacin-containing triple therapy (400 mg moxifloxacin once daily, and 20 mg of rabeprazole and 1 g of amoxicillin twice daily). H. pylori status was evaluated using the (13)C-urea breath test 4 wk later, after treatment completion. The eradication rates were determined by intention-to-treat and per-protocol analyses. RESULTS: In total, 60 and 38 patients received 1-wk and 2-wk moxifloxacin-containing triple therapy, respectively. The intention-to-treat and per-protocol eradication rates were 56.7% (95%CI: 45.0-70.0) and 59.6% (95%CI: 46.6-71.7) in the 1-wk group and 76.3% (95%CI: 63.2-89.5) and 80.6% (95%CI: 66.7-91.9) in the 2-wk group (P = 0.048 and 0.036, respectively). All groups had good compliance (95% vs 94.9%). Neither group showed serious adverse events, and the proportions of patients experiencing mild side effects were not significantly different (21.1% vs 13.9%). Clinical factors such as age, sex, alcohol and smoking habits, comorbidities, and presence of gastric or duodenal ulcer did not influence the eradication therapy efficacy. The efficacy of second-line eradication therapy did not differ significantly according to the first-line regimen. CONCLUSION: Two-week moxifloxacin-containing triple therapy showed better efficacy than a 1-wk regimen after non-bismuth quadruple therapy failure.

Efficacy of moxifloxacin-based sequential and hybrid therapy for first-line Helicobacter pylori eradication.

AIM: To evaluate the efficacy of moxifloxacin-based sequential therapy (MBST) versus hybrid therapy as a first-line treatment for Helicobacter pylori (H. pylori) infection. METHODS: From August 2014 to January 2015, 284 patients with confirmed H. pylori infection were randomized to receive a 14-d course of MBST (MBST group, n = 140) or hybrid (Hybrid group, n = 144) therapy. The MBST group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 7 d, followed by 20 mg rabeprazole and 500 mg metronidazole twice daily, and 400 mg moxifloxacin once daily for 7 d. The Hybrid group received 20 mg rabeprazole and 1 g amoxicillin twice daily for 14 d. In addition, the Hybrid group received 500 mg metronidazole and 500 mg clarithromycin twice daily for the final 7 d. Successful eradication of H. pylori infection was defined as a negative (13)C-urea breath test 4 wk after the end of treatment. Patient compliance was defined as "good" if drug intake was at least 85%. H. pylori eradication rates, patient compliance with treatment, and adverse event rates were evaluated. RESULTS: The eradication rates in the intention-to-treat (ITT) analysis were 91.4% (128/140; 95%CI: 90.2%-92.9%) in the MBST group and 79.2% (114/144; 95%CI: 77.3%-80.7%) in the Hybrid group (P = 0.013). The eradication rates in the per-protocol (PP) analysis were 94.1% (128/136; 95%CI: 92.9%-95.6%) in the MBST group and 82.6% (114/138; 95%CI: 80.6%-84.1%) in the Hybrid group (P = 0.003). The H. pylori eradication rate in the MBST group was significantly higher than that of the Hybrid group for both the ITT (P = 0.013) and the PP analyses (P = 0.003). Both groups exhibited full compliance with treatment (MBST/Hybrid group: 100%/100%). The rate of adverse events was 11.8% (16/136) and 19.6% (27/138) in the MBST and Hybrid group, respectively (P = 0.019). The majority of adverse events were mild-to-moderate in intensity; none were severe enough to cause discontinuation of treatment in either group. CONCLUSION: MBST was more effective and led to fewer adverse events than hybrid therapy as a first-line treatment for H. pylori infection.

[Efficacy and Safety of New Prokinetic Agent Benachio Q Solution® in Patients with Postprandial Distress Syndrome Subtype in Functional Dyspepsia: A Single-center, Randomized, Double-blind, Placebo-controlled Pilot Study].

BACKGROUND/AIMS: Functional dyspepsia (FD) is a gastrointestinal disorder in which the patient suffers from chronic abdominal symptoms despite the absence of organic disease. Benachio Q solution (soln.)® is a new prokinetic herbal medicine. The aim of the present study is to determine the efficacy and safety of Benachio Q soln.® in patients with postprandial distress syndrome (PDS) subtype in FD. METHODS: A single-center, randomized, double-blind, placebo-controlled pilot study was performed in 20 patients with PDS. Patients were assigned to receive either Benachio Q soln.® or placebo three times a day. After 4 weeks of treatment, the data on response rates, symptoms severity of PDS and gastric emptying time were analyzed to evaluate its efficacy. Adverse events, laboratory tests and vital sign were analyzed to assess its safety. RESULTS: Nine patients were assigned to Benachio group and 10 patients to placebo group. The response rate after 4 weeks was 44.4% and 20.0% in Benachio and placebo group, respectively (p=0.350). The response rate during the first week in Benachio group was better compared to that of placebo group with marginal difference (33.3% vs. 0.0%, p=0.087). Changes of severity score in early satiety on second and third week were -1.8 ± 0.6, -1.9 ± 0.4 and -1.3 ± 0.5, -1.4 ± 0.6 in Benachio and placebo group, respectively (p=0.059 vs. p=0.033). No adverse event was observed. CONCLUSIONS: The new herbal drug, Benachio Q soln.® seems to improve the symptoms of PDS subtype in FD and could be used safely. Further larger trial is needed in the future.

Efficacy of moxifloxacin-based sequential therapy for first-line eradication of Helicobacter pylori infection in gastrointestinal disease.

AIM: To evaluate the efficacy of 14-d moxifloxacin-based sequential therapy as first-line eradication treatment of Helicobacter pylori (H. pylori) infection. METHODS: From December 2013 to August 2014, 161 patients with confirmed H. pylori infection randomly received 14 d of moxifloxacin-based sequential group (MOX-ST group, n = 80) or clarithromycin-based sequential group (CLA-ST group, n = 81) therapy. H. pylori infection was defined on the basis of at least one of the following three tests: a positive (13)C-urea breath test; histologic evidence of H. pylori by modified Giemsa staining; or a positive rapid urease test (CLOtest; Delta West, Bentley, Australia) by gastric mucosal biopsy. Successful eradication therapy for H. pylori infection was defined as a negative (13)C-urea breath test four weeks after the end of eradication treatment. Compliance was defined as good when drug intake was at least 85%. H. pylori eradication rates, patient compliance with drug treatment, adverse event rates, and factors influencing the efficacy of eradication therapy were evaluated. RESULTS: The eradication rates by intention-to-treat analysis were 91.3% (73/80; 95%CI: 86.2%-95.4%) in the MOX-ST group and 71.6% (58/81; 95%CI: 65.8%-77.4%) in the CLA-ST group (P = 0.014). The eradication rates by per-protocol analysis were 93.6% (73/78; 95%CI: 89.1%-98.1%) in the MOX-ST group and 75.3% (58/77; 95%CI: 69.4%-81.8%) in the CLA-ST group (P = 0.022). Compliance was 100% in both groups. The adverse event rates were 12.8% (10/78) and 24.6% (19/77) in the MOX-ST and CLA-ST group, respectively (P = 0.038). Most of the adverse events were mild-to-moderate in intensity; there was none serious enough to cause discontinuation of treatment in either group. In multivariate analysis, advanced age (≥ 60 years) was a significant independent factor related to the eradication failure in the CLA-ST group (adjusted OR = 2.13, 95%CI: 1.97-2.29, P = 0.004), whereas there was no significance in the MOX-ST group. CONCLUSION: The 14-d moxifloxacin-based sequential therapy is effective. Moreover, it shows excellent patient compliance and safety compared to the 14-d clarithromycin-based sequential therapy.

Efficacy of 7-Day and 14-Day Bismuth-Containing Quadruple Therapy and 7-Day and 14-Day Moxifloxacin-Based Triple Therapy as Second-Line Eradication for Helicobacter pylori Infection.

BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen. METHODS: From August 2004 to October 2012, a total of 949 patients (mean age, 54.32±12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the (13)C-urea breath test, rapid urease test or histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.

Helicobacter pylori eradication with moxifloxacin-containing therapy following failed first-line therapies in South Korea.

AIM: To investigate moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori (H. pylori) infection following failed first-line treatment. METHODS: The sample included 312 patients for whom first-line treatment failed between January 2008 and May 2013; 27 patients were excluded, and a total of 285 patients received 7- or 14-d moxifloxacin-containing triple therapy as second-line treatment for H. pylori infection. First line regimens included 7-d standard triple (n = 172), 10-d bismuth-containing quadruple (n = 28), 14-d concomitant (n = 37), or 14-d sequential (n = 48) therapy. H. pylori status was evaluated using (13)C-urea breath testing 4 wk later, after completion of the treatment. The primary outcome was the H. pylori eradication rate analyzed using intention-to-treat (ITT) and per protocol (PP) analyses. The secondary outcome was the occurrence of serious adverse events. Demographic and clinical factors were analyzed using Student's t-tests and Pearson's χ(2) tests according to first- and second-line regimens. A P value of less than 0.05 was considered statistically significant. RESULTS: The eradication rate of moxifloxacin-containing triple therapy was 68.4% (ITT; 95%CI: 62.8-73.5) and 73.9% (PP; 95%CI: 68.3-78.8). The eradication rate was significantly higher with 14 d compared to 7 d of treatment (77.5% vs 62.5%, P = 0.017). Peptic ulcer patients had a higher eradication rate than the patients without ulcers (82.9% vs 70.6%, P = 0.046). The demographic and clinical characteristics were not significantly different between the groups according to first-line therapies. ITT and PP analyses of the moxifloxacin-containing triple therapy indicated the following eradication rates: 70.9% (95%CI: 63.8-77.2) and 77.2% (95%CI: 70.1-83.1) for standard triple; 67.9% (95%CI: 51.5-84.2) and 67.9% (95%CI: 51.5-84.2) for bismuth-containing quadruple; 60.4% (95%CI: 46.3-73.0) and 70.7% (95%CI: 54.0-80.9) for sequential; and 67.6% (95%CI: 51.5-80.4) and 67.6%(95%CI: 51.5-80.4) for concomitant therapy. There were no statistically significant differences in the efficacy of the first-line regimens (P = 0.492). The most common adverse event was diarrhea. There were no serious adverse events and no significant differences in the frequency of side effects between the first- and second-line regimens (28.7% vs 26.1%, respectively). CONCLUSION: Moxifloxacin-containing triple therapy as second-line treatment resulted in low eradication rates. There were no differences in the efficacy between the first-line regimens in South Korea.

Factors affecting first-line triple therapy of Helicobacter pylori including CYP2C19 genotype and antibiotic resistance.

BACKGROUND: Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori (H. pylori) has decreased. AIMS: To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade. METHODS: We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202 H. pylori-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method. RESULTS: In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (P = 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2-17.2%, P = 0.003) and clarithromycin (23.2-37.3%, P = 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2%, P = 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m(2), amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95% CI, 5.58-29.18; P < 0.001). CONCLUSIONS: An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of H. pylori.