Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Extremity risk factors of sepsis for gastrointestinal endoscopy in patients with liver cirrhosis.

BACKGROUND: Liver cirrhosis is a well-known risk factor of sepsis after emergent gastrointestinal (GI) endoscopy. Elective GI endoscopy before living donor liver transplantation (LDLT), however, may also carry the septic risk among these patients. METHODS: This retrospective study reviewed the medical records of 642 cirrhotic recipients who underwent GI endoscopy from 2008 to 2016. We analyzed the incidence and risk factors of post-endoscopy sepsis during 2008-2012 (experience cohort). Our protocol changed after 2013 (validation cohort) to include antibiotic prophylaxis. RESULTS: In experience cohort, 36 cases (10.5%) of the 342 LDLT candidates experienced sepsis within 48 h after endoscopy. The sepsis rate was significantly higher in patients with hepatic decompensation than patients without (22.2% vs. 9.6% vs. 2.6% in Child C/B/A groups respectively; ×2 = 20.97, P < 0.001). Using multivariate logistic regression analysis, the factors related to post-endoscopy sepsis were the Child score (OR 1.46; 95% CI 1.24-1.71), Child classes B and C (OR 3.80 and 14.13; 95% CI 1.04-13.95 and 3.97-50.23, respectively), hepatic hydrothorax (OR 4.85; 95% CI 1.37-17.20), and use of antibiotic prophylaxis (OR 0.08; 95% CI 0.01-0.64). In validation cohort, antibiotics were given routinely, and all cases of hepatic hydrothorax (n = 10) were drained. Consequently, 4 (1.3%) episodes of sepsis occurred among 300 LDLT candidates, and the incidence was significantly lower than before (1.3% vs. 10.5%, P < 0.001). CONCLUSIONS: Patients with decompensated cirrhosis and hepatic hydrothorax have higher risk of sepsis following endoscopy. In advanced cirrhotic patients, antibiotic prophylaxis and drainage of hydrothorax may be required to prevent sepsis before elective GI endoscopy.

The effectiveness and safety of vedolizumab induction for moderate to severe ulcerative colitis for Asia patient: A real practice observational study.

BACKGROUND: The use of biologic agents has become the cornerstone of therapy for moderate to severe IBD. Few studies have investigated the efficacy of vedolizumab (VDZ) induction for ulcerative colitis (UC) in Asian patients in a real practice setting. AIMS: To evaluate the efficacy and safety of VDZ induction therapy for moderate to severe UC in Taiwan. METHODS: This was a retrospective and observational study. Selected moderate to severe UC patients received VZD 300 mg i.v. at weeks 0, 2, and 6 as induction therapy. Mayo scores were calculated to evaluate the efficacy. RESULTS: A total of 37 patients with UC who received VDZ and completed the induction therapy at Chang Gung Memorial Hospital (2017/10-2021/5) were included. The mean age was 46.5 year-old and the male to female ratio was 1:1 (19/18). 81.8% of the patients were biologic-naive. At weeks 8-10, a clinical response, clinical remission and endoscopic remission with VDZ induction therapy were achieved in 56.8% (21/37), 32.4% (12/37) and 58.3% (7/12) of the patients, respectively. 54.1% (20/37) were able to taper off at week 8. Overall, only 10.8% (4/37) of the patients were primary non-responders during induction therapy. No obvious VDZ-related severe adverse events were noted. Overall, 58.9% (11/19) of the patients relapsed after stopping VDZ, and the relapse rate after VDZ discontinuation was 42.1% (8/19) within first 6 months and 52.6% (10/19) within the first year. CONCLUSION: In real-world experience, induction therapy with VDZ showed promising clinical benefits and safety profile for patients with UC.

Eradication Rates for Esomeprazole and Lansoprazole-Based 7-Day Non-Bismuth Concomitant Quadruple Therapy for First-Line Anti-Helicobacter pylori Treatment in Real World Clinical Practice.

PURPOSE: Non-bismuth concomitant quadruple therapy is commonly administered in Taiwan, achieving an acceptable efficacy as a first-line anti-Helicobacter pylori treatment. This study compared the eradication rates between esomeprazole- and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line anti-H. pylori treatment. PATIENTS AND METHODS: This study included 206 H. pylori-infected naïve patients between July 2016 and February 2019. The patients were prescribed with either a 7-day non-bismuth containing quadruple therapy (esomeprazole, 40 mg twice daily; amoxicillin, 1 g twice daily; and metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily for 7 days [EACM group]; lansoprazole, 30 mg twice daily; amoxicillin, 1 g twice daily; metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily [LACM group]). Then, the patients were asked to perform urea breath tests 8 weeks later. RESULTS: The eradication rates in the EACM group were 86.1% (95% confidence interval [CI], 77.8%-92.2%) and 90.6% (95% CI, 82.9%-95.6%) in the intention-to-treat (ITT) and the per-protocol (PP) analyses, respectively. Moreover, the eradication rates in the LACM group were 90.1% (95% CI, 82.6%-95.2%) and 92.6% (95% CI, 85.5%-96.9%) in the ITT and the PP analyses, respectively. Consequently, the LACM group exhibited more diarrhea patients than the EACM group (7.1% versus 1.0%, p = 0.029), but all symptoms were mild. Univariate analysis in this study showed that metronidazole-resistant strains were the clinical factor affecting the eradications (95.3% versus 78.9%, p = 0.044). Moreover, a trend was observed in dual clarithromycin- and metronidazole-resistant strains (91.5% versus 66.7%, p = 0.155). CONCLUSION: The eradication rates between esomeprazole and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line H. pylori treatment were similar in this study. Both could achieve a > 90% report card in the PP analysis.

The efficacies of non-bismuth containing quadruple therapies in the treatment of first-line anti-Helicobacter pylori across 4-year time interval with changing antibiotics resistance.

BACKGROUND: Non-bismuth containing quadruple therapy (concomitant therapy) is an alternative treatment for Helicobacter pylori (H. pylori) eradication with increasing clarithromycin-resistant strains over times. This study compared the efficacies of non-bismuth containing quadruple therapy (concomitant therapy) in the treatment of first-line anti-Helicobacter Pylori between two time intervals (January 2013 to June 2014 and June 2016 to December 2017). METHODS: H. pylori-infected patients were recruited in the intention-to-treat (ITT analysis) and divided into EACM-A group (enrolled from January 2013 to June 2014, N = 98) and EACM-B group (enrolled from June 2016 to December 2017, N = 99). Patients were prescribed with 7-day esomeprazole 40 mg bid., clarithromycin 500 mg bid., amoxicillin 1 g bid. and metronidazole 500 mg bid. Ninety patients and 93 patients were analyzed in the per protocol (PP) analysis (8 and 6 patients lost follow-up in each group). Urea breath tests were performed 4-8 weeks thereafter. RESULTS: The eradication rates for EACM-A and EACM-B groups were 87.8% (95% confidence interval [CI] = 79.7%-93.5%) and 84.8% (95% CI = 76.2%-91.2%) (p = 0.55) in intention-to-treat (ITT) analysis; 95.6% (95% CI = 89.1%-98.8%) and 90.3% (95% CI = 82.4%-95.5%) (p = 0.17) in per protocol (PP) analysis. The adverse event rates were 16.7% vs. 10.8% in the 2 groups (p = 0. 0.24). The antibiotic resistance rates between the 2 groups were amoxicillin (0%), tetracycline (0%); clarithromycin (11.8% vs. 17.8%, p = 0.46); metronidazole (32.4% vs. 33.3%, p = 0.93) and levofloxacin (14.7% vs. 37.8%, p = 0.02). CONCLUSION: The success rate of 7-days concomitant therapy encountered an approximately 5% decrease across 4-year time interval (2013-2017) with the changes of clarithromycin resistance from 11.8% to 17.8% in Taiwan.

Autonomic impairment in treatment-naive patients with chronic hepatitis B and C infections.

BACKGROUND: Peripheral neuropathy is not an uncommon manifestation in patients with chronic hepatitis. The role of cryoglobulin (CG) in neuropathy in patients with chronic hepatitis remains controversial. There is limited information about the autonomic neuropathy in chronic hepatitis. This study aimed to evaluate autonomic function in treatment-naive patients with chronic hepatitis B or hepatitis C infection and to elucidate the association between autonomic neuropathy and CG in these patients. METHODS: A total of 29 treatment-naive patients with chronic, yet mild degrees of hepatitis B or C infection were evaluated for autonomic function, including those in the sympathetic sudomotor, cardiovagal, and adrenergic domains, to compare with the control subjects. The autonomic impairment was graded using the Composite Autonomic Scoring Scale. Then, association analyses between autonomic parameters/scores and CG were performed. RESULTS: Patients with chronic hepatitis B or C infection had significantly worse autonomic function than control subjects, especially in the sudomotor and cardiovagal domains. The autonomic manifestations in cases with and without CG were similar. There was no significant difference in autonomic dysfunction between patients with hepatitis B and C infections. CONCLUSION: The study demonstrated that autonomic neuropathy was not uncommon in patients with chronic hepatitis B or C infection. There was no association between autonomic neuropathy and CG.

Risks of adverse events for users of proton-pump inhibitors plus aspirin or clopidogrel in patients with aspirin-related ulcer bleeding.

BACKGROUND AND AIM: Clopidogrel is widely prescribed for patients with of aspirin-related upper gastrointestinal bleeding (UGIB) history. This study aimed to compare the risk of a major adverse cardiovascular event (MACE), UGIB, and mortality between aspirin and clopidogrel in patients at risk of bleeding. METHODS: We analyzed adult patients at high risk of UGIB following aspirin-related bleeding for secondary MACE prevention between 2000 and 2012. Secondary prevention was for those patients who had ever been hospitalized for cardiovascular disease and reused aspirin or changed to clopidogrel after discharge. Study endpoints were recurrence of MACE, UGIB, and death in 90 days of follow-up. The associations between study outcomes and the use of clopidogrel (vs aspirin) were analyzed. RESULTS: Among 947 eligible patients, 653 reused aspirin (in combination with a proton-pump inhibitor), and 294 were treated with clopidogrel (in combination with a proton-pump inhibitor) after discharge for UGIB. Compared with aspirin treatment, clopidogrel showed an increased risk of MACE (adjusted hazard ratio [aHR] 1.65; 95% confidence interval [CI] 0.87-3.12) and UGIB (aHR 1.25; 95% CI 0.66-2.36), but without statistical significance in 90 days' follow-up. Clopidogrel use was associated with greater than four times the risk of any cause of mortality (aHR 4.84; 95% CI 1.59-14.75), but the significance did not hold in propensity score-matched cohort analysis (P = 0.06). CONCLUSIONS: A nonsignificant difference between clopidogrel and aspirin for short-term MACE prevention as well as UGIB recurrence was found in the present study. Further research to assess 90-day mortality would assist clinical decision making.

Tongue diagnosis indices for gastroesophageal reflux disease: A cross-sectional, case-controlled observational study.

Traditional Chinese medicine tongue diagnosis can mirror the status of the internal organ, but evidence is lacking regarding the accuracy of tongue diagnosis to gastroesophageal reflux disease (GERD). This study was to investigate the association between GERD and tongue manifestation, and whether tongue imaging could be initial diagnosis of GERD noninvasively.We conducted a cross-sectional, case-controlled observational study at Kaohsiung Chang Gung Memorial Hospital in Taiwan from January 2016 to September 2017. Participants aged over 20 years old with GERD were enrolled and control group without GERD were matched by sex. Tongue imaging were acquired with automatic tongue diagnosis system, then followed by endoscope examination. Nine tongue features were extracted, and a receiver operating characteristic (ROC) curve, analysis of variance, and logistic regression were used.Each group enrolled 67 participants. We found that the saliva amount (P = .009) and thickness of the tongue's fur (P = .036), especially that in the spleen-stomach area (%) (P = .029), were significantly greater in patients with GERD than in those without. The areas under the ROC curve of the amount of saliva and tongue fur in the spleen-stomach area (%) were 0.606 ±â€Š0.049 and 0.615 ±â€Š0.050, respectively. Additionally, as the value of the amount of saliva and tongue fur in the spleen-stomach area (%) increased, the risk of GERD rose by 3.621 and 1.019 times, respectively. The tongue fur in the spleen-stomach area (%) related to severity of GERD from grade 0 to greater than grade B were 51.67 ±â€Š18.72, 58.10 ±â€Š24.60, and 67.29 ±â€Š24.84, respectively.The amount of saliva and tongue fur in the spleen-stomach area (%) might predict the risk and severity of GERD and might be noninvasive indicators of GERD. Further large-scale, multi-center, randomized investigations are needed to confirm the results.Trial registration: NCT03258216, registered August 23, 2017.

A comparison between dexlansoprazole modified release-based and lansoprazole-based nonbismuth quadruple (concomitant) therapy for first-line Helicobacter pylori eradication: a prospective randomized trial.

PURPOSE: Steadily maintaining high intra-gastric PH is the major factor for successful Helicobacter pylori (H.pylori) eradication. It is important to search for a stronger PPI. Dexlansoprazole MR is a dual delayed release formulation PPI taken once daily which is capable of maintaining longer duration of high intra-gastric PH. It is very effective in treating gastroesophageal disease but reports on H, pylori eradication is very rare. This study sought to compare dexlansoprazole MR-based concomitant treatment and lansoprazole-based concomitant treatment in H. pylori infection and to investigate the factors that affect the eradication rates. METHODS: Two hundred two participants with H. pylori infection were included and randomly assigned to seven days of dexlansoprazole MR-based concomitant therapy (dexlansoprazole MR 60 mg once daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily; DACM group) or a seven days of lansoprazole-based concomitant therapy (lansoprazole 30 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily, and metronidazole 500 mg twice daily; LACM group). The participants were asked to perform urea breath tests eight weeks later. RESULTS: The eradication rates in the DACM group were 86.1% [95% confidence interval (CI): 77.8%-92.2%] in the ITT analysis and 90.6% (95% CI: 82.9%-95.6%) in the PP analysis, respectively, as compared with 90.1% (95% CI: 82.6%-95.2%) and 92.6% (95% CI: 85.5%-96.9%) (p=0.384 and p=0.572, respectively) in the LACM group for the same analyses. The adverse event rates were 11.5% in the DACM group and 10.2% in the LACM group (p=0.779). CONCLUSION: As a first-line H. pylori treatment regimen, dexlansoprazole MR-based concomitant therapy attained a successful eradication rate of 90%, which was non inferior to that of lansoprazole-based concomitant treatment. CLINICALTRIALSGOV IDENTIFIER: NCT03829150.

First-line Helicobacter pylori eradication rates are significantly lower in patients with than those without type 2 diabetes mellitus.

Purpose: To assess the difference of the first-line therapy for Helicobacter pylori in patients with or without type 2 diabetes (DM) and to investigate the clinical factors influencing treatment outcomes. Patients and methods: In total, 719 patients with H. pylori infection were treated with 7-day standard first-line triple therapy, of whom 182 did and 537 did not have DM. Propensity score matched at a 1:2 ratio - for age, sex and body mass index was performed for the two groups, yielding a DM group with 147 patients and a non-DM group with 249 matched controls for analysis. Urea breath test was performed 6-8 weeks after treatment. Clinical and laboratory parameters were collected for identifying factors associated with failed eradication. Results: H. Pylori was eradicated in 74.1% (95% confidence interval [CI] =66.2-81.0) of the DM group and 85.3% (95% CI =80.8-89.4) of the non-DM group (p=0.005). Of 51 gastric biopsy samples cultured for H. pylori, 41 were positive. In the DM group, the rates of resistance to amoxicillin, clarithromycin, levofloxacin, and tetracycline were 0%, 50.0%, 50.0% and 0%, respectively. In the non-DM group, the comparable proportions were 2.9%, 17.1%, 22.9%, and 0%, respectively. Univariate analysis revealed that DM (Odds ratio [OR], 1.771, 95% CI, 1.167-2.668, p=0.006), clarithromycin resistance (OR, 15.273; 95% CI, 1.687-138.269; p=0.015), and amoxicillin resistance (OR, 4.672; 95% CI, 2.431-8.979; p<0.001) were independently associated with failure to eradicate H. pylori. Multivariate analysis showed that clarithromycin resistance was the major factor independently associated with failure of eradication (OR, 25.472; 95% CI, 1.549-418.956; p=0.023). Conclusions: First-line H. pylori eradication rates in patients with DM were significantly lower than in those without DM, although neither group achieved >90% eradication.

The efficacy of limited endoscopic sphincterotomy plus endoscopic papillary large balloon dilation for removal of large bile duct stones.

BACKGROUND: The removal of large bile duct stones (> 15 mm) by conventional endoscopic sphincterotomy (EST) and endoscopic papillary balloon dilation (EPBD) can be challenging, requiring mechanical lithotripsy (ML) in addition to EST or EPBD. The primary complication of ML is basket and stone impaction, which can lead to complications such as pancreatitis and cholangitis. The present study aims to investigate the efficacy of limited EST plus endoscopic papillary large balloon dilation (EST-EPLBD) for large bile duct stone extraction with an extent of cutting < 1/2 the length of the papillary mound. METHODS: We enrolled 185 patients with ≥15 mm bile duct stones who received EST, EPLBD and limited EST-EPLBD treatment from January 1, 2010 to February 28, 2018, at Kaohsiung Chang Gung Memorial Hospital (Kaohsiung, Taiwan). All patients were categorized into three groups: EST group (n = 31), EPLBD group (n = 96), and limited EST-EPLBD group (n = 58). The primary outcome variables were the success rate of complete stone removal and complications. RESULTS: The limited EST-EPLBD group exhibited a higher success rate of the first-session treatment compared with the EST and EPLBD groups (98.3% vs. 83.9% vs. 86.5%; P = 0.032) but required a longer procedure time (32 (12-61) min vs. 23.5 (17-68) min vs. 25.0 (14-60) min; P = 0.001). The need for ML during the procedure was 4 (12.9%) in the EST group, 10 (10.4%) in the EPLBD group and 2 (3.4%) in the limited EST-EPLBD group. Post-procedure bleeding in the EST group was more common than that in the limited EST-EPLBD group (9.7% vs. 0%; P = 0.038). Furthermore, dilated bile duct was the only risk factor for bile duct stone recurrence in the limited EST-EPLBD group. CONCLUSIONS: Limited EST-EPLBD exhibits a higher success rate but requires marginally longer procedure time for the first-session treatment. Furthermore, dilated bile duct is the only risk factor for bile duct stone recurrence in patients undergoing limited EST-EPLBD.

Clinical efficacy of 60-mg dexlansoprazole and 40-mg esomeprazole after 24 weeks for the on-demand treatment of gastroesophageal reflux disease grades A and B: a prospective randomized trial.

Purpose: Research comparing the clinical efficacy of dexlansoprazole and esomeprazole has been limited. This study aims to compare the clinical efficacy of single doses of dexlansoprazole (modified-release 60 mg) and esomeprazole (40 mg) after 24-week follow-up in patients with mild erosive esophagitis. Methods: We enrolled 86 adult GERD subjects, randomized in a 1:1 ratio to two sequence groups defining the order in which they received single doses of dexlansoprazole (n=43) and esomeprazole (n=43) for 8 weeks as initial treatment. Patients displaying complete symptom resolution (CSR) by the end of initial treatment (8 weeks) were switched to on-demand therapy until the end of 24 weeks. Follow-up endoscopy was performed either at the end of 24 weeks or when severe reflux symptoms occurred. Five patients were lost to follow-up, leaving 81 patients (dexlansoprazole, n=41; esomeprazole, n=40) in the per-protocol analysis. Results: The GERDQ scores at 4-, 8-, 12-, 16-, 20-, and 24-week posttreatment were less than the baseline score. The CSR, rate of symptom relapse, days to symptom resolution, sustained healing rate of erosive esophagitis, treatment failure rate, and the number of tablets taken in 24 weeks were similar in both groups. The esomeprazole group had more days with reflux symptoms than the dexlansoprazole group (37.3±37.8 vs 53.9±54.2; P=0.008). In the dexlansoprazole group, patients exhibited persistent improvement in the GERDQ score during the on-demand period (week 8 vs week 24; P<0.001) but not in the esomeprazole group (week 8 vs week 24; P=0.846). Conclusions: This study suggests that the symptom relief effect for GERD after 24 weeks was similar for dexlansoprazole and esomeprazole. Dexlansoprazole exhibited fewer days with reflux symptoms in the 24-week study period, with better persistent improvement in the GERDQ score in the on-demand period. (ClinicalTrials. gov number: NCT03128736).

Bridging the Gap between Advancements in the Evolution of Diagnosis and Treatment towards Better Outcomes in Achalasia.

Over the past few decades, there was an encouraging breakthrough in bridging the gap between advancements in the evolution of diagnosis and treatment towards a better outcome in achalasia. The purpose of this review is to provide updated knowledge on how the current evidence has bridged the gap between advancements in the evolution of diagnosis and treatment of esophageal achalasia. The advent of high-resolution manometry and standardization based on the Chicago classification has increased early recognition of the disease. These 3 clinical subtypes of achalasia can predict the outcomes of patients, and the introduction of POEM has revolutionized the choice of treatment. Previous evidence has shown that laparoscopic Heller myotomy (LHM) and anterior fundoplication were considered the most durable treatments for achalasia. Based on the current evidence, POEM has been evolving as a promising strategy and is effective against all 3 types of achalasia, but the efficacy of POEM is based on short- and medium-term outcome studies from a limited number of centers. Types I and II achalasia respond well to POEM, LHM, and PD, while most studies have shown that type III achalasia responds better to POEM than to LHM and PD. In general, among the 3 subtypes of achalasia, type II achalasia has the most favorable outcomes after medical or surgical therapies. The long-term efficacy of POEM is still unknown. The novel ENDOFLIP measures the changes in intraoperative esophagogastric junction dispensability, which enables a quantitative assessment of luminal patency and sphincter distension; however, this technology is in its infancy with little data to date supporting its intraoperative use. In the future, identifying immunomodulatory drugs and the advent of stem cell therapeutic treatments, including theoretically transplanting neuronal stem cells, may achieve a functional cure. In summary, it is important to identify the clinical subtype of achalasia to initiate target therapy for these patients.

A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-Helicobacter pylori treatment in Taiwan: a prospective randomized trial.

BACKGROUND: The first-line eradication rate of standard triple therapy for Helicobacter pylori infection has declined to <80%, and alternative therapies with >90% success rates are needed. Inconsistent eradication rates were reported for proton pump inhibitor- and amoxicillin-containing high-dose dual therapy. OBJECTIVES: We performed a prospective, randomized controlled study to assess the efficacy of esomeprazole- and amoxicillin-containing high-dose dual therapy and investigated the influencing clinical factors. PATIENTS AND METHODS: We recruited 240/278 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 14 day high-dose dual therapy (esomeprazole 40 mg three times daily and amoxicillin 750 mg four times daily for 14 days; EA group) or 7 day non-bismuth quadruple therapy (esomeprazole 40 mg twice daily, clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and metronidazole 500 mg twice daily for 7 days; EACM group). Urea breath tests were followed up 8 weeks later. RESULTS: The eradication rates for the EA and EACM groups were 91.7% (95% CI = 85.3%-96.0%) and 86.7% (95% CI = 79.3%-92.2%) (P = 0.21) in ITT analysis; and 95.7% (95% CI = 90.2%-98.6%) and 92.0% (95% CI = 85.4%-96.3%) (P = 0.26) in PP analysis. The adverse event rates were 9.6% versus 23.0% in the two groups (P = 0.01). The H. pylori culture positivity rate was 91.8%. The antibiotic resistance rates were amoxicillin, 0%; clarithromycin, 14.6%; and metronidazole, 33.7%. CONCLUSIONS: A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy achieves a high eradication rate as first-line anti-H. pylori therapy, comparable to that with 7 day non-bismuth quadruple therapy but with fewer adverse events.

Effect of extracorporeal low-energy shock wave on diabetic gastroparesis in a rat model.

BACKGROUND AND AIM: Delayed gastric emptying occurs in more than 50% of chronic diabetic patients, and this is associated with significant impairments in quality of life. Traditional therapy for delayed gastric emptying has focused on supportive treatment, and there is no significant effective therapy. The effect of low-energy shock wave on gastric motility is never studied. We investigated low-energy shock wave on gastric motility in a diabetic rat model. METHODS: Twenty-eight male Wistar rats were studied and separated in three groups in randomized order as control, diabetic rats received shock wave, and diabetic rats received the sham procedure. Antral area and motility were recorded using the transabdominal ultrasound. Blood was taken for measurement of gastric motility peptides. Subjects were killed for immunohistochemical stain analysis of enteric plexus of the stomach. RESULTS: We successfully induced 20 diabetic rats and set ultrasound for measuring rat gastric contract and emptying model and demonstrated that 6 weeks of low-energy shock wave could promote gastric contraction and emptying in diabetic rats. Moreover, we demonstrated that shock wave could increase defecation and feces and decrease serum cholesterol and triglycerol. However, no effect on glycohemoglobin and gastric motility peptides was recorded. In the immunohistochemical staining, shock wave increased expression of gastric myenteric neuron plexus. CONCLUSION: Low-energy shock wave can increase gastric contraction and emptying by activating axonal regeneration and increasing myenteric plexus, but not related with motility peptides.

Efficacy of a 14-day quadruple-therapy regimen for third-line Helicobacter pylori eradication.

PURPOSE: To assess the efficacy of amoxicillin, tetracycline, high-dose metronidazole, and a proton-pump inhibitor for third-line Helicobacter pylori eradication. METHODS: We enrolled 70 consecutive patients who had registered, failed to respond to two rounds of H. pylori eradication, and undergone endoscopy for H. pylori culture. Seven patients were lost to follow-up. Patients were treated according to the results of antibiotic-susceptibility testing reports (cultured group, n=39). Those who failed the H. pylori culture were prescribed 14-day quadruple therapy containing esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three times daily (empirical group, n=24). A follow-up urea breath test was performed 8 weeks later. RESULTS: Antibiotic-resistance rates were 79.5% (clarithromycin), 94.9% (levofloxacin), 66.7% (metronidazole), 2.6% (amoxicillin), and 0 (tetracycline). Eradication rates attained by the cultured and empirical group were 89.7% (95% CI 72.7%-97.1%) and 58.3% (95% CI 36.6%-77.9%) in per-protocol analysis (P=0.004) and 81.4% (95% CI 66.6%-91.6%) and 51.8% (95% CI 31.9%-71.3%) in intention-to-treat analysis (P=0.014), respectively. Culture-guided therapy was the only clinical factor influencing the efficacy of H. pylori eradication (OR 0.16, 95% CI 0.04-0.60; P=0.006). Despite the high metronidazole-resistance rate (66.7%) after two treatment failures, the eradication rate in patients with this condition was 84%. CONCLUSION: Empirical 14-day modified quadruple therapy is not acceptable as an alternative third-line rescue H. pylori treatment. The success rate of third-line susceptibility-guided treatment was near 90%. This report is valuable as a reminder to medical practitioners that rather than a try-and-see approach, susceptibility-guided therapy should always be considered whenever possible for patients who have undergone several treatment failures.

Prognostic factors of patients with gastroenteropancreatic neuroendocrine neoplasms.

There is an increasing trend in the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) worldwide. The aim of the present study was to identify the prognostic factors of patients with GEP-NENs. A cross-sectional, retrospective chart review study was conducted among patients with pathologically proven GEP-NENs between January 2003 and December 2016 at Kaohsiung Chung-Gung Memorial Hospital. A total of 97 patients who met the inclusion criteria were included (male/female = 56/41, age: 57.7 ± 15.4 years). The presentation, clinical characteristics, and disease outcomes were reviewed and analyzed. The most common primary site of the GEP-NENs was the rectum (49.5%), followed by the pancreas (17.5%), duodenum (11.3%), stomach (10.3%), colon (6.2%), and appendix (5.2%), and most GEP-NENs were hormonally nonfunctional (94.8%). There were 56 tumors classified as G1 neuroendocrine tumors (NETs), 9 as G2 NETs, and 14 as G3 neuroendocrine carcinoma (NEC). Metastasis was found in 15 patients (15%). Curative treatments, such as surgery or endoscopic resection, were performed in 83.5% of patients (n = 81). The mean overall survival duration was 107.2 ± 7.8 months. The estimated 3- and 5-year overall survival rates for all patients were 84% and 82%, respectively. Logistic regression analysis showed that large tumor size, non-rectal NENs, high histopathological grading, lymphatic metastases and distant metastases were associated with poor survival. This study suggested that the presence of lymphatic or distant metastases at diagnosis is an independent risk factor for poor prognosis in patients with GEP-NENs.

Extracellular galectin-3 facilitates colon cancer cell migration and is related to the epidermal growth factor receptor.

We previously found that galectin-3 enhanced DLD-1 cell migration through the K-Ras-Raf-Erk1/2 pathway, but the effect of extracellular galectin-3 on cancer cell migration and its interaction with the epidermal growth factor receptor (EGFR) remained unknown. We aimed to determine the effect of extracellular galectin-3 on colon cancer cell migration and its correlation with the EGFR expression. Western blotting was performed to analyze galectin-3 secretion, shRNA was used to stably knock down galectin-3 expression and a migration assay was performed to evaluate colon cancer cell migration. Tissues from eighty patients with four different stages of colon cancer were obtained and compared to normal colon tissue. The galectin-3 knockdown colon cancer cells exhibited decreased migration, which was restored by recombinant galectin-3. An EGFR blocking antibody decreased colon cancer cell migration. The addition of recombinant galectin-3 increased phosphorylated EGFR expression within minutes and enhanced the internalization of the EGFR from the cell membrane to the cytoplasm, particularly upon EGF stimulation. Extracellular galectin-3 increased colon cancer cell migration, which correlated with the EGFR. Targeting galectin-3 may have a synergistic effect on EGFR-targeted therapy.

Carcinoembryonic antigen as a marker of radioresistance in colorectal cancer: a potential role of macrophages.

BACKGROUND: We sought to identify the carcinoembryonic antigen (CEA) as a marker of radioresistance in rectal cancer. METHODS: From July 1997 to January 2008, 104 patients with stage II or III rectal cancer who were treated with post-operative radiotherapy (PORT) were included in this study. The doses of radiotherapy ranged from 45 to 54.6 Gy. The CEA levels were measured before surgery. We analyzed the actuarial rates of overall survival (OS), distant metastasis (DM), and local recurrence (LR) using Kaplan-Meier curves. Multivariate analyses were performed with Cox regression models. We used THP-1 monocyte cell lines for macrophage differentiation (M0, M1 or M2). The RNA extracted from the macrophages was analyzed via a genomic method in the core laboratory. The radiosensitivities of CEA-rich LS1034 cells were compared between cells with and without the conditioned media from CEA-stimulated macrophages. RESULTS: Preoperative CEA levels ≥10 ng/mL were independent predictive factors for OS (p = 0.005), DM (p = 0.026), and LR (p = 0.004). The OS rates among the patients with pretreatment CEA levels < 10 ng/mL and ≥10 ng/mL were 64.5% and 35.9% (p = 0.004), respectively. The corresponding rates of DM were 40.6% and 73.1% (p = 0.024). The corresponding rates of LR were 6.6% and 33.9% (p = 0.002). In the M0 macrophages, exogenous CEA elicited a dose-response relationship with M2 differentiation. In the CEA-stimulated M0 cells, some mRNAs were upregulated by as much as 5-fold, including MMP12, GDF15, and JAG1. In the CEA-stimulated M2 cells, a 4-fold up-regulation of GADD45G mRNA was noted. The conditioned media from the CEA-stimulated M2 cells elicited an increase in the numbers of LS180, SW620, and LS1034 cells after irradiation. CEA caused the M2 differentiation of the macrophages. CONCLUSION: Pretreatment CEA levels ≥10 ng/mL are a significant risk factor for OS, DM, and LR following PORT for rectal cancer. CEA causes radioresistance in the presence of M2 macrophages. More comprehensive examinations prior to surgery and intensive adjuvant therapy are suggested for patients with CEA levels ≥10 ng/mL. Further studies of these mechanisms are needed.

Tongue diagnosis indices for upper gastrointestinal disorders: Protocol for a cross-sectional, case-controlled observational study.

BACKGROUND: Upper gastrointestinal disorders are common in clinical practice, for example, gastritis, peptic ulcer disease, and gastroesophageal reflux disease. Panendoscopy or upper gastrointestinal endoscopy is viewed as the primary tool for examining the upper gastrointestinal mucosa, and permitting biopsy and endoscopic therapy. Although panendoscopy is considered to be a safe procedure with minimal complications, there are still some adverse effects, and patients are often anxious about undergoing invasive procedures. Traditional Chinese medicine tongue diagnosis plays an important role in differentiation of symptoms because the tongue reflects the physiological and pathological condition of the body. The automatic tongue diagnosis system (ATDS), which noninvasively captures tongue images, can provide objective and reliable diagnostic information. METHODS: This protocol is a cross-sectional, case-controlled observational study investigating the usefulness of the ATDS in clinical practice by examining its efficacy as a diagnostic tool for upper gastrointestinal disorders. Volunteers over 20 years old with and without upper gastrointestinal symptoms will be enrolled. Tongue images will be captured and the patients divided into 4 groups according to their panendoscopy reports, including a gastritis group, peptic ulcer disease group, gastroesophageal reflux disease group, and healthy group. Nine primary tongue features will be extracted and analyzed, including tongue shape, tongue color, tooth mark, tongue fissure, fur color, fur thickness, saliva, ecchymosis, and red dots. OBJECTIVES: The aim of this protocol is to apply a noninvasive ATDS to evaluate tongue manifestations of patients with upper gastrointestinal disorders and examine its efficacy as a diagnostic tool.