Comparison of Vonoprazan versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding after Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial.

BACKGROUND & AIMS: High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aims to compare the efficacy of vonoprazan versus PPI for preventing high-risk PU rebleeding after hemostasis. METHODS: A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20-mg BID for 3 days, then 20-mg OD for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/hour for 3 days, then omeprazole 20-mg BID for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3-and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. RESULTS: Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable among the two groups. The 30-day rebleeding rate in vonoprazan and PPI groups were 7.1% (7/98) and 10.4% (10/96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference= -3.3; 95% confidence interval = -11.2, 4.7; P<0.001). The 3-day and 7-day rebleeding rates in vonoprazan group remained noninferior to PPI (P< 0.001 by Farrington and Manning test). All secondary outcomes were also comparable between the two groups. CONCLUSION: In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI.

Treatment outcomes in patients with globus: A randomized control trial of psychoeducation, neuromodulators, and proton pump inhibitors.

BACKGROUND: Globus is a persistent or intermittent nonpainful sensation of a lump or foreign body, which markedly affect patient's quality of life. Treatment options for globus are limited and unsatisfying. This study aims to compare the effects of cognitive-behavioral-theory-based psychoeducation (CBT), neuromodulators (NMD), and proton pump inhibitor (PPI) on treatment outcomes in patients with globus. METHODS: Eligible patients were randomly received CBT, 0.5 mg flupenthixol and 10 mg melitracen; NMD, or omeprazole 20 mg; PPI, for 4 weeks. The primary endpoint was the reduction in symptom scores; Glasgow Edinburgh Throat Scale (GETS). The secondary endpoints included treatment efficacy on Reflux Symptom Index (RSI), Hospital Anxiety Depression Scale (HADS), and quality of life (QoL) based on a 36-item short-form health survey (SF-36). Treatment compliance and adverse effects were recorded. KEY RESULTS: Forty patients were completed study. Baseline characteristics between the groups were comparable. By the end of treatment, both CBT and NMD provided greater reduction in GETS than PPI (CBT vs PPI; 6.46 ± 8.56 vs 0.21 ± 5.42; p = 0.031, NMD vs PPI; 6.92 ± 9.85 vs 0.21 ± 5.42; p = 0.036). The improvement of RSI, HADS, and SF-36 among the groups was similar. Neuromodulators caused more adverse events. CONCLUSIONS & INFERENCES: Both CBT and NMD provided equally effective treatment and better than PPI in patients with globus determined by the reduction in GETS. The improvement in RSI, HADS, and QoL of the three groups was not different. Given less of adverse effect than NMD, CBT should be considered as a substantial treatment.

"MURAL" model to predict bleeding from mural-based lesions in potential small bowel bleeding may improve diagnostic capability and decrease cost.

In potential small bowel bleeding, video capsule endoscopy (VCE) is excellent to detect mucosal lesions, while mural-based lesions are better detected by computed tomography enterography (CTE). A predictive tool to identify mural-based lesions should guide selecting investigations. In this retrospective study, we developed and validated the "MURAL" model based on logistic regression to predicts bleeding from mural-based lesions. Cost-effectiveness analysis comparing diagnostic strategy among VCE, CTE, and MURAL model was performed. Of 296 patients, 196 and 100 patients were randomly included in the derivative and validation cohorts, respectively. The MURAL model comprises 5 parameters: age, presence of atherosclerosis, chronic kidney disease, antiplatelet use, and serum albumin level. The area under the receiver operating characteristic curve was 0.778 and 0.821 for the derivative and validation cohorts, respectively. At a cutoff value of 24.2%, the model identified mural-based lesions with 70% sensitivity and 83% specificity in the validation cohort. Cost-effectiveness analysis revealed that application of the MURAL model demonstrated a comparable missed lesion rate but had a lower missed tumor rate, and lower cost compared to VCE strategy. The model for predicting mural-based lesions provide some guidance in investigative decision-making, which may improve diagnostic efficiency and reduce costs.

Thailand guideline 2020 for medical management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most prevalent and bothersome functional gastrointestinal disorders worldwide, including in Thailand. After a decade of the first Thailand GERD guideline, physician and gastroenterologist encountered substantially increase of patients with GERD. Many of them are complicated case and refractory to standard treatment. Concurrently, the evolution of clinical characteristics as well as the progression of investigations and treatment have developed and changed tremendously. As a member of Association of Southeast Asian Nations, which are developing countries, we considered that the counterbalance between advancement and sufficient economy is essential in taking care of patients with GERD. We gather physicians from university hospitals, as well as internist and general practitioners who served in rural area, to make a consensus in this updated version of GERD guideline focusing in medical management of GERD. This clinical practice guideline was constructed adhering with standard procedure. We categorized the guideline in to four parts including definition, investigation, treatment, and long-term follow up. We anticipate that this guideline would improve physicians' proficiency and help direct readers to choose investigations and treatments in patients with GERD wisely. Moreover, we wish that this guideline would be applicable in countries with limited resources as well.

Continuous Infusion of Fluid Hydration Over 24 Hours Does Not Prevent Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Aggressive intravenous fluid hydration, by administering 3500 mL of lactated Ringer's solution (LRS) in 9 h with a peri-procedural bolus, reduces post-ERCP pancreatitis (PEP) incidence. A concern of this strategy is adverse events related to volume overload; however, the impact of fluid hydration over an extended period without a bolus on PEP is unknown. AIM: To assess the effect of continuous infusion of high-volume fluid at a constant rate over 24 h on PEP incidence and severity. METHODS: Two-hundred patients were randomly assigned (1:1) to receive either 3600 mL of LRS in 24 h starting 2 h before the ERCP (high-volume group) or maintenance fluid hydration calculated by the Holliday-Segar method (control group). RESULTS: The mean age of the patients was 50.6 ± 11.6 years. The predominant indications were choledocholithiasis (48%) and malignancies (32%). Patient demographics and PEP risk factors were similar in both groups. Patients in the high-volume group received significantly more fluid than the control group (3600 vs. 2413 ml, P < 0.001). PEP incidence was not different between the high-volume and the control group (14% vs. 15%; relative risk 0.93: 95% CI 0.48-1.83, P = 0.84). There were no differences in moderate to severe PEP (3% vs. 4%; relative risk 0.75: 95% CI, 0.17-3.27, P = 1.00). Subgroup analysis did not show a benefit in high-risk patients. Only one patient in the control group developed peripheral edema. CONCLUSIONS: An infusion of high-volume hydration over 24 h is not sufficient to provide optimal hydration for PEP prevention. CLINICAL TRIAL REGISTRY NUMBER: No. NCT02821546.

Value of age and alarm features for predicting upper gastrointestinal malignancy in patients with dyspepsia: an endoscopic database review of 4664 patients in Thailand.

OBJECTIVE: Age and alarm features are commonly used as indicators for endoscopy in dyspeptic patients; however, the age cut-off and the predictive value of these parameters for identifying upper gastrointestinal (UGI) malignancies are uncertain. DESIGN: Cross-sectional study. SETTING: Data were extracted from the Gastrointestinal Endoscopy Centre of Siriraj Hospital, Thailand, during 2005-2011. PARTICIPANTS: Consecutive patients underwent a first-time upper endoscopy for dyspepsia. Patients with previous surgery, suspected UGI malignancy by imaging, or indefinite biopsy results on prior examination were excluded. MAIN OUTCOME MEASURES: Alarm features included dysphagia, unintentional weight loss, GI bleeding/anaemia, and persistent vomiting. The diagnostic performance of each alarm feature and different age cut-off values were evaluated. RESULTS: A total of 4664 patients (mean age: 52.0±14.4 years, 66% female) were included. Alarm symptoms were presented in 21.6%. The prevalence of active Helicobacter pylori infection was 26.3%. Fifty-eight (1.2%) patients had UGI malignancy. The prevalence of malignancy significantly increased with increasing age (0.6% in patients aged <50 years, and 1.8% in patients aged >60 years (p<0.001)). Cancer was found in two patients aged <50 years who did not have alarm features. Patients with alarm features had a higher prevalence of malignancy (OR 22.3, 95% CI 10.5 to 47.4; p<0.001) than those without. The pooled sensitivity, specificity, positive predictive value and negative predictive value of alarm features for UGI malignancy were 87.0%, 79.1%, 4.7% and 99.8%, respectively. Among all age groups, persistent vomiting had a positive likelihood ratio (PLR) >10, while dysphagia and GI bleeding/anaemia had a PLR >10 in patients <50 years old. CONCLUSION: Despite the overall limited value of age and alarm features, persistent vomiting, dysphagia, and GI bleeding/anaemia are strong predictors for malignancy in patients aged <50 years. Without these symptoms, cancer prevalence is negligible; thus, they are worthy guidance for endoscopic evaluation in this age group.

Consensus statements and recommendations on the management of mild-to-moderate gastroesophageal reflux disease in the Southeast Asian region.

This paper reports the proceedings from the first consensus meeting on the management of mild-to-moderate gastroesophageal reflux disease (GERD) in the Southeast Asian (SEA) region. Seventeen statements were drawn up by a steering committee that focused on epidemiology, mechanism of action, diagnostic investigations, and treatment. Voting on the recommendations used the Delphi method with two rounds of voting among the 10 panel members. The consensus panel agreed that GERD is mostly a mild disease in the SEA region with predominantly non-erosive reflux disease (NERD). Complicated GERD and Barrett's esophagus are infrequently seen. The panel recommended endoscopy in patients with alarm or refractory symptoms but cautioned that the incidence of gastric cancer is higher in SEA. pH and impedance measurements were not recommended for routine assessment. The acid pocket is recognized as an important pathogenic factor in GERD. Lifestyle measures such as weight reduction, avoidance of smoking, reduction of alcohol intake, and elevation of the head of the bed were recommended but strict avoidance of specific foods or drinks was not. Alginates was recommended as the first-line treatment for patients with mild-to-moderate GERD while recognizing that proton-pump inhibitors (PPIs) remained the mainstay of treatment of GERD. The use of alginates was also recommended as adjunctive therapy when GERD symptoms were only partially responsive to PPIs.

Negative Video Capsule Endoscopy Had a High Negative Predictive Value for Small Bowel Lesions, but Diagnostic Capability May Be Lower in Young Patients with Overt Bleeding.

Background: Patients with potential small bowel bleeding (PSBB) who have negative results of video capsule endoscopy (VCE), clinical course, rate of rebleeding, and missed lesions with their predictors are essential for further management decision. Methods: This retrospective study included patients presenting with PSBB who had negative VCE findings between January 2008 and December 2016. All patients had to have at least two years of follow-up data to be included. Patients with <2 years of follow-up in their medical record were interviewed by telephone to determine if any unrecorded rebleeding episodes occurred. Results: One hundred forty-two patients were included. The mean age was 60.9 years, and 52.8% were male. Eighty-one patients presented with overt bleeding. The median duration of follow-up was 5.08 years. During the follow-up period, 30 patients experienced rebleeding. The cumulative rate of rebleeding at 1, 2, and 5 years was 10.0%, 14.3%, and 22.4%, respectively. Multivariate analysis showed nonsteroidal anti-inflammatory drugs (NSAIDs) and presentation of overt bleeding to be independent predictors of rebleeding. There were only nine small bowel lesions (6.3%) missed by VCE. These nine patients, compared with others, were significantly younger and tended to present with overt bleeding. Conclusion: Rebleeding was not uncommon in PSBB after negative VCE; however, the rate of missing small bowel lesions was low. Nonetheless, further investigations may be considered in young patients who present with overt bleeding.

Successful advanced third-space endoscopic surgery by per-oral endoscopic myotomy (Z-POEM) for Zenker's diverticulum: A case report and review of literature.

INTRODUCTION: Zenker's diverticulum is a rare condition caused by herniation of the mucosa at the pharyngoesophageal junction, resulting in dysphagia. Third-space endoscopic surgery now plays an important role in its management, facilitating precise surgery with good outcomes. The aim of report is to demonstrate technical steps and outcomes of per-oral endoscopic myotomy (Z-POEM). PRESENTATION OF CASE: We report two male patients presented with dysphagia. Esophagograms revealed Zenker's diverticula of 2.1 and 2.0 cm, respectively, and diagnostic gastroscopy showed the diverticula to be 17 cm from the incisors, with tight, thick septal muscle. A 2-cm mucosal incision was made with a triangle-tipped knife, and submucosal tunneling was created by spray coagulation. The gastroscope was advanced into the submucosal space of the esophageal lumen and the diverticulum site until the bottom of the diverticulum could be clearly identified. The septal muscle was completely divided, immediately allowing the gastroscope to pass through easily, and the mucosal defect was reapproximated with hemoclips. DISCUSSION: As compared Z-POEM to previous technique; endoscopic septotomy, staple-assisted diverticulotomy, or open neck surgery, Z-POEM is less recurrent of symptoms and complications. Different types of endoscopic knife and lifting materials were used, but all provided the same outcomes. Most of the cases use though-the-scope clips to close the mucosal defect. CONCLUSION: Z-POEM provided precise treatment and complete view of the entire septal muscle can helps to avoid inadequate myotomy.

Successful Closure of a Benign Refractory Tracheoesophageal Fistula Using an Over-the-Scope Clip after Failed Esophageal Stent Placement and Surgical Management.

Tracheoesophageal fistulas (TEFs) have traditionally been managed surgically, but the endoscopic approach is widely performed as a less invasive alternative. Different closure techniques have been proposed with inconsistent results. An over-the-scope clip (OTSC) appears to be a reasonable option, but long-term results have not been well defined. We report the long-term outcomes of a complex case of successful closure of a benign refractory TEF using an OTSC after failed surgical management and esophageal stent placement.

Preoperative endoscopic predictors of severe submucosal fibrosis in colorectal tumors undergoing endoscopic submucosal dissection.

Background and study aims Endoscopic submucosal dissection (ESD) enables en bloc removal of colorectal neoplasms regardless of size. Submucosal fibrosis is a significant factor for technical difficulty and poor outcomes. We assessed the predictive factors for severe submucosal fibrosis and the ESD outcomes. Patients and methods Patients undergoing ESD from January 2006 to September 2017 were retrospectively reviewed. The degree of submucosal fibrosis was classified into three types: no fibrosis (F0), mild fibrosis (F1), and severe fibrosis (F2). F0 and F1 cases were grouped as non-severe fibrosis for comparison with the severe fibrosis group. Predictors of severe submucosal fibrosis and ESD outcomes were evaluated. Results ESD was performed in 524 lesions (60 % male; mean age, 67.8 years). Eighty lesions with severe fibrosis (15.3 %) were observed. The overall en bloc resection rate and curative resection rate were 94.3 % and 77.7 %, respectively. Rates of en bloc resection (91.2 % vs. 94.8 %, P  = 0.2) and perforation (7.5 % vs. 5.6 %, P  = 0.45) were no different between severe fibrosis and non-severe fibrosis groups. However, incidences of non-curative resection and low resection speed were significantly higher in the severe fibrosis group. Among protruding lesions, tumor height and volume were significantly greater in the severe counterparts. A diameter ≥ 40 mm, endoscopic finding of the tumor beyond fold, and fold convergence were independent risk factors for severe fibrosis. Conclusions Severe submucosal fibrosis is a significant risk factor for non-curative resection and a long procedural time. Tumor size and morphology might help to predict the severity of fibrosis.

Thailand Dyspepsia Guidelines: 2018.

The management of dyspepsia in limited-resource areas has not been established. In 2017, key opinion leaders throughout Thailand gathered to review and evaluate the current clinical evidence regarding dyspepsia and to develop consensus statements, rationales, levels of evidence, and grades of recommendation for dyspepsia management in daily clinical practice based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. This guideline is mainly focused on the following 4 topics: (1) evaluation of patients with dyspepsia, (2) management, (3) special issues (overlapping gastroesophageal reflux disease/irritable bowel syndrome and non-steroidal anti-inflammatory drug/aspirin use), and (4) long-term follow-up and management to provide guidance for physicians in Thailand and other limited-resource areas managing such patients.

Consensus and contentious statements on the use of probiotics in clinical practice: A south east Asian gastro-neuro motility association working team report.

The concept of consuming microorganisms in the treatment of a medical condition and in health maintenance has gained much attraction, giving rise to an abundance of medical claims and of health supplements. This study identified relevant clinical questions on the therapeutic use of probiotics and reviewed the literature in irritable bowel syndrome, inflammatory bowel disease, impaired intestinal immunity, liver disease, intestinal infections, and common childhood digestive disorders. Statements were developed to address these clinical questions. A panel of experienced clinicians was tasked to critically evaluate and debate the available data. Both consensus and contentious statements are presented to provide to clinicians a perspective on the potential of probiotics and importantly their limitations.

Helicobacter pylori management in ASEAN: The Bangkok consensus report.

Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.

Efficacy and safety of nortriptyline in functional dyspepsia in Asians: A randomized double-blind placebo-controlled trial.

BACKGROUND AND AIM: Current treatments of functional dyspepsia (FD) are unsatisfied. Tricyclic antidepressants alter visceral hypersensitivity and brain-gut interaction. We assessed the efficacy and safety of nortriptyline in patients with FD. METHODS: Patients diagnosed with FD according to Rome III criteria who failed to respond to proton pump inhibitor and prokinetic treatment were randomly assigned to either once daily 10-mg nortriptyline or placebo. The primary endpoint was the rate of responders defined as > 50% reduction in dyspepsia symptom score after 8 weeks of treatment. The secondary endpoints were improvement in quality of life as assessed by 36-Item Short Form Health Survey score and safety. RESULTS: Sixty-one patients (nortriptyline 28 and placebo 33) were enrolled. Dyspepsia symptom score and duration of symptoms were balanced at entry between both groups. Eight and seven patients in nortriptyline and placebo groups were lost to follow up. Seven patients withdrew due to mild adverse events (nortriptyline 1 and placebo 6). Overall, 19 with nortriptyline and 20 with placebo completed the study. Patients receiving nortriptyline did not achieve higher response rate than those in placebo in both intention-to-treat (53.6% vs 57.6%, P = 0.75) and per-protocol (76.5% vs 73.7%, P = 1.00) analyses. Nortriptyline did not provide improvement in quality of life. The mean difference was 3.8 (P = 0.36) and 0.88 (P = 0.86) by intention-to-treat and 2.9 (P = 0.57) and 3.5 (P = 0.57) by per-protocol analyses in physical and mental component, respectively. All adverse events were minor and similar in both groups. CONCLUSION: Nortriptyline was not superior to placebo in management of patients with FD.

A Prospective Blinded Comparison of Video Capsule Endoscopy Versus Computed Tomography Enterography in Potential Small Bowel Bleeding: Clinical Utility of Computed Tomography Enterography.

GOALS: To compare the efficacy of video capsule endoscopy (VCE) with computed tomography enterography (CTE) in potential small bowel (SB) bleeding, and to identify factors predictive of a high diagnostic yield for CTE. BACKGROUND: In potential SB bleeding, CTE potentially detects some lesions missed by VCE, but few data have determined its clinical utility. STUDY: Consecutive patients with potential SB bleeding were prospectively enrolled. All underwent VCE and CTE within a 1-week interval. Definitive diagnoses were made by surgery or enteroscopy, except when a strategy of VCE and conservative management was suitable. The diagnostic yields and sensitivities of each investigation were measured. RESULTS: Fifty-two patients were recruited (41 with overt and 11 with occult bleeding); 36 received a definitive diagnosis. The diagnostic yields and sensitivities of VCE and CTE were 59.6% and 30.8% (P=0.004), and 72.2% and 44.4% (P=0.052), respectively. The combined sensitivity of VCE and CTE (88.9%) was significantly greater than VCE (P=0.03) or CTE (P<0.01) alone. VCE was better for ulcers, enteritis, and angiodysplasia, whereas CTE was better for tumors and Meckel diverticula. Age below 40 years and severe bleeding were associated with a higher diagnostic yield for CTE [odds ratios (95% confidence interval)=7.3 (1.04-51.4), P=0.046 and 6.1 (1.4-25.5), P=0.014, respectively]. CONCLUSIONS: Both investigations complement each other in the diagnosis of potential SB bleeding. CTE should be considered when VCE is negative. Age below 40 years and severe bleeding were independent predictors of a higher diagnostic yield for CTE.

The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study.

BACKGROUND/AIMS: To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. METHODS: A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. RESULTS: The mean decreases in the total symptom score at 4 weeks were estimated to be -18.1±13.8 in the combination therapy group and -15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were -8.4±6.6 in the combination therapy group and -6.8±5.9 in the monotherapy group (p=0.009). CONCLUSIONS: Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.