Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

BACKGROUND AND AIM: Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS: We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS: We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS: A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Association of self-reported and objective sleep disturbance with the spectrum of gastroesophageal reflux disease.

STUDY OBJECTIVES: The relationship between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) is complex. We aimed to determine the association of self-reported and objective sleep parameters with diverse manifestations of the GERD spectrum. METHODS: We prospectively recruited 561 individuals who underwent an electrocardiogram-based cardiopulmonary coupling for OSA screening during a health check-up. All participants received the Reflux Disease Questionnaire and an upper endoscopy to determine the presence of troublesome reflux symptoms and erosive esophagitis (EE). Sleep quality was evaluated by the Pittsburgh Sleep Quality Index and sleep dysfunction was defined as a Pittsburgh Sleep Quality Index score > 5. OSA was defined as a cardiopulmonary coupling-derived apnea-hypopnea index exceeding 15 events/h. Comparisons were made between participants on the GERD spectrum with respect to their various self-reported and objective sleep parameters. RESULTS: Among the 277 patients with GERD (49.4%), 198 (35.3%) had EE. Patients with GERD had higher PSQI scores (6.99 ± 3.97 vs 6.07 ± 3.73, P = .005) and a higher prevalence of sleep dysfunction (60.6% vs 49.6%, P = .009). Patients with EE had a higher prevalence of OSA (42.9% vs 33.9%, P = .034). Along the GERD spectrum, symptomatic patients with EE had the highest PSQI scores and prevalence of sleep dysfunction (70.7%), while asymptomatic patients with EE had the highest prevalence of OSA (44%). CONCLUSIONS: Our findings indicate a high prevalence of sleep dysfunction among individuals with GERD. Furthermore, patients on the GERD spectrum are prone to experiencing a range of self-reported and objective sleep disturbances. CITATION: Hu K-Y, Tseng P-H, Hsu W-C, et al. Association of self-reported and objective sleep disturbance with the spectrum of gastroesophageal reflux disease. J Clin Sleep Med. 2024;20(6):911-920.

Effect of peroral endoscopic myotomy on growth and esophageal motility for pediatric esophageal achalasia.

BACKGROUND/PURPOSE: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, has been shown to be effective and safe for both adult and pediatric patients. However, studies on its application in children in Taiwan and its impact on growth and esophageal motility are lacking. METHODS: We conducted a retrospective study on consecutive pediatric patients who were diagnosed with esophageal achalasia at National Taiwan University Hospital and underwent POEM during 2015-2022. Disease characteristics and treatment outcomes were analyzed. RESULTS: Ten patients (age 16.9 ± 3.1 years), nine newly diagnosed and one previously treated with pneumatic dilatation, underwent POEM for achalasia (type I/II/III: 3/7/0). Average symptom duration before diagnosis was 19.4 ± 19.9 months, mean POEM procedure time was 83.6 ± 30.7 min, and clinical success (Eckardt score ≤3) was achieved in all patients. Eight patients experienced mild adverse events during POEM, but none required further endoscopic or surgical intervention. Over a mean follow-up period of 3.7 ± 1.6 years, mean Eckardt score decreased significantly from 5.7 ± 2.4 to 1.1 ± 0.7 (p = 0.0001). The BMI z-score also increased significantly after POEM (p = 0.023). Five patients received follow-up high-resolution impedance manometry (HRIM), and all had improved lower esophageal sphincter resting pressures (p = 0.011), body contractility, and bolus transit (p = 0.019). CONCLUSION: POEM is an effective and safe treatment for pediatric achalasia in Taiwan. Early diagnosis and treatment with POEM may help to restore esophageal function and nutrition status in children.

Characteristics of Esophageal Motility and Associated Symptom Profiles in Patients with Esophageal Diverticulum: A Study Based on High-Resolution Impedance Manometry.

BACKGROUND: Esophageal diverticulum (ED) is an uncommon structural disorder with heterogenous manifestations and elusive pathophysiology. Our aim was to investigate esophageal motility and associated symptom profiles in patients with ED based on high-resolution impedance manometry (HRIM). METHODS: Consecutive patients with ED referred to our motility laboratory between 2015 to 2022 were identified in our electronic database. All patients were evaluated based on an upper endoscopy, HRIM, and standardized symptom questionnaires. Patients with ED were further stratified into upper, middle, and lower (epiphrenic) cases. Esophageal motility was evaluated with HRIM and the updated Chicago Classification v4.0. RESULTS: Twenty-four patients with ED (9 upper, 4 middle, and 11 epiphrenic) were analyzed. Patients with ED were generally older (mean: 65 ± 13.3 years) and predominantly women (58.3%). Most ED cases were unilaterally located (95.8%) and left-side predominant (62.5%). Mean symptom duration was 20 months (range: 1-120) and the most common symptoms were dysphagia (70.8%) and regurgitation (37.5%). Erosive esophagitis was noted in 16 patients (69.6%), while barium stasis was noted in 5 patients (20.8%). Fourteen patients (58.3%) were diagnosed with esophageal motility disorders using HRIM, with achalasia being the most common diagnosis (n = 5, 20.8%). Patients with epiphrenic diverticulum had significantly higher symptom scores and achalasia prevalence. CONCLUSION: Patients with ED tended to be older and was associated with a high prevalence of EMD. A multi-disciplinary evaluation, including complete anatomical and motility surveys, may help clarify the underlying pathophysiology and tailor further treatment strategies.

Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: two multicentre, open-label, randomised controlled, non-inferiority trials.

BACKGROUND: Helicobacter pylori infection is an important causal factor of gastric cancer and peptic ulcer disease and is associated with immune thrombocytopenic purpura and functional dyspepsia. In H pylori strains, point mutations in the 23S rRNA and gyrA genes are associated with clarithromycin resistance and levofloxacin resistance, respectively. Whether the efficacy of molecular testing-guided therapy is non-inferior to that of susceptibility testing-guided therapy for H pylori eradication is unclear. Therefore, we aimed to compare the efficacy and safety of molecular testing-guided therapy and traditional culture-based susceptibility testing-guided therapy in first-line and third-line treatment of H pylori infection. METHODS: We did two multicentre, open-label randomised trials in Taiwan. In trial 1 (done at seven hospitals), treatment-naive individuals infected with H pylori who were aged 20 years or older were eligible for study inclusion. In trial 2 (done at six hospitals), individuals aged 20 years or older who failed treatment after two or more eradication therapies for H pylori infection were eligible for enrolment. Eligible patients were randomly assigned (1:1) to receive either molecular testing-guided therapy or susceptibility testing-guided therapy. The randomisation sequence was generated by computer using permuted block randomisation with a block size of 4. All investigators were masked to the randomisation sequence. Clarithromycin and levofloxacin resistance were determined by agar dilution test for measuring minimum inhibitory concentrations in the susceptibility testing-guided therapy group, and by PCR and direct sequencing for detection of 23S rRNA and gyrA mutations in the molecular testing-guided therapy group. Study participants received clarithromycin sequential therapy, levofloxacin sequential therapy, or bismuth quadruple therapy according to the resistance status to clarithromycin and levofloxacin. The 13C-urease breath test was used to determine the status of H pylori infection at least 6 weeks after eradication therapy. The primary outcome was the eradication rate by intention-to-treat analysis. The frequency of adverse effects was analysed in patients with available data. The prespecified margins for non-inferiority were 5% for trial 1 and 10% for trial 2. The trials are ongoing for post-eradication follow-up and registered with ClinicalTrials.gov, NCT03556254 for trial 1, and NCT03555526 for trial 2. FINDINGS: Between March 28, 2018, and April 23, 2021, 560 eligible treatment-naive patients with H pylori infection were recruited and randomly assigned to the molecular testing-guided therapy group or the susceptibility testing-guided therapy group in trial 1. Between Dec 28, 2017, and Oct 27, 2020, 320 eligible patients with refractory H pylori infection were recruited and randomly assigned to the molecular testing-guided therapy group or the susceptibility testing-guided therapy group in trial 2. 272 men and 288 women were recruited for trial 1, and 98 men and 222 women were recruited for trial 2. In first-line H pylori treatment, infection was eradicated in 241 (86%, 95% CI 82-90) of 280 patients in the molecular testing-guided therapy group and 243 (87%, 83-91) of 280 patients in the susceptibility testing-guided therapy group by intention-to-treat analysis (p=0·81). In third-line H pylori treatment, infection was eradicated in 141 (88%, 83-93) of 160 patients in the molecular testing-guided therapy group and 139 (87%, 82-92) of 160 patients in the susceptibility testing-guided therapy group by intention-to-treat analysis (p=0·74). The difference in the eradication rate between the molecular testing-guided therapy group and the susceptibility testing-guided therapy group was -0·7% (95% CI -6·4 to 5·0; non-inferiority p=0·071) in trial 1 and 1·3% (-6·0 to 8·5; non-inferiority p=0·0018 in trial 2 by intention-to-treat analysis. We found no difference in adverse effects across both treatment groups in trial 1 and trial 2. INTERPRETATION: Molecular testing-guided therapy was similar to susceptibility testing-guided therapy in first-line therapy and non-inferior to susceptibility testing guided therapy in third-line treatment of H pylori infection, supporting the use of molecular testing-guided therapy for H pylori eradication. FUNDING: Ministry of Science and Technology of Taiwan, and Centre of Precision Medicine of the Higher Education Sprout Project by the Ministry of Education of Taiwan.

Characteristics of the esophageal microbiome in patients with achalasia and its changes before and after peroral endoscopic myotomy: A pilot study.

BACKGROUND AND AIM: Achalasia often presents with chronic food stasis and fermentation in the esophageal lumen, which may lead to alterations of the esophageal microbiome, with associated mucosal inflammation and dysplastic changes. The study aims to evaluate the characteristics of the esophageal microbiome in achalasia and changes of the esophageal microbiome before and after peroral endoscopic myotomy (POEM). METHODS: This is a prospective case-control study. This study enrolled patients with achalasia and asymptomatic subjects as control group. Endoscopic brushing for esophageal microbiome collection was performed in all subjects, with additional follow-up endoscopy and brushing 3 months after POEM in achalasia patients. The composition of the esophageal microbiome was determined and compared between (1) achalasia patients and asymptomatic controls and (2) achalasia patients before and after POEM. RESULTS: Thirty-one achalasia patients (mean age 53.5 ± 16.2 years; male 45.2%) and 15 controls were analyzed. We observed a distinct esophageal microbial community structure in achalasia patients, with increased Firmicutes and decreased Proteobacteria when compared with the control group at the phylum level. The discriminating enriched genera in achalasia patients were Lactobacillus, followed by Megasphaera and Bacteroides, and the amount of Lactobacillus was associated with the severity of achalasia. Twenty patients were re-examined after POEM, and a high prevalence of erosive esophagitis (55%) was noted, alongside an increase in genus Neisseria and decrease in Lactobacillus and Bacteroides. CONCLUSIONS: The altered esophageal microenvironment in achalasia leads to dysbiosis with a high abundance of genus Lactobacillus. Increased Neisseria and decreased Lactobacillus were observed after POEM. The long-term effect of microbial changes warrants further study.

Second-line levofloxacin-based quadruple therapy versus bismuth-based quadruple therapy for Helicobacter pylori eradication and long-term changes to the gut microbiota and antibiotic resistome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters. METHODS: We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured by 13C urea breath test 6 weeks after second-line treatment according to both intention-to-treat (ITT) and per-protocol analysis. The microbiota composition and antibiotic resistome of faecal samples collected at baseline (before treatment) and at 2 weeks, 8 weeks, and 1 year after eradication therapy was profiled by shotgun metagenomic sequencing and 16S rRNA gene sequencing. The frequency of adverse effects and changes in the gut microbiota and antibiotic resistome were assessed in all participants with available data. The trial is complete and registered with ClinicalTrails.gov, NCT03148366. FINDINGS: Between Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10-10) at week 2, which were restored to pretreatment level by week 8. The resistance rates of Escherichia coli and Klebsiella pneumonia to levofloxacin, ciprofloxacin, ampicillin (ampicillin-sulbactam for K pneumonia), and various cephalosporins were significantly increased in the EAML14 group compared with in the BQ10 group at week 2, which were restored to pretreatment levels and showed no significant differences at week 8 and 1 year. The frequency of any adverse effects was significantly higher after BQ10 therapy (211 [77%] of 273 participants) than after EAML14 therapy (134 [48%] of 277; p<0·0001). INTERPRETATION: We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy. FUNDING: The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Positive and negative impact of anti-reflux mucosal intervention on gastroesophageal reflux disease.

BACKGROUND: Anti-reflux mucosal intervention (ARMI), including anti-reflux mucosectomy (ARMS) and anti-reflux mucosal ablation (ARMA), is a promising endoscopic treatment for gastroesophageal reflux disease (GERD). Few studies reported a detailed analysis of the objective reflux parameters. METHODS: Patients with chronic PPI-dependent GERD and receiving ARMI were prospectively enrolled. Comprehensive clinical symptom profiles, endoscopy results, and 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring were collected and analyzed before and 3 months after ARMI. RESULTS: Twenty-three patients undergoing ARMI (11 ARMS and 12 ARMA) were enrolled. The median (IQR) operative time and post-procedure stays were 50 (46-56) min and 2 (2-2) days without major complications. 73.9% of patients reported subjective global improvement. A significant decrease in the total reflux symptom index score was noted from 12 (5-19) to 8 (4-12) (P = 0.010). The esophageal acid exposure time (AET) significantly decreased from 4.6 (2.8-6.9) to 2.1 (1.1-5.6) (P = 0.013), and the number of acid refluxes and DeMeester score were significantly reduced. Three patients (13%) had increased AET (3.4% to 6.1%, 6.3% to 15.4%, and 3.2% to 5.6%); however, all reported global improvement and two patients could discontinue PPI subjectively. One patient (4.3%) had worsened erosive esophagitis and reflux symptoms. 56.5% of patients stopped PPI. CONCLUSIONS: ARMI is generally effective and safe in PPI-dependent patients. However, possible negative effects of ARMI exist in some patients; further application of MII-pH is necessitated to evaluate the treatment response after ARMI and avoid the detrimental effect of PPI discontinuation. Graph.

Clinical Characteristics and Associated Psychosocial Dysfunction in Patients With Functional Dysphagia: A Study Based on High-Resolution Impedance Manometry and Rome IV Criteria.

INTRODUCTION: The pathophysiology of functional dysphagia as defined by the updated Rome IV criteria is complex and remains largely unknown. We aimed to investigate its clinical characteristics and its association with psychosocial comorbidities. METHODS: Consecutive patients referred to our motility laboratory for evaluation of esophageal dysphagia were identified. All patients were assessed with upper endoscopy, high-resolution impedance manometry, and validated symptom questionnaires. Data from those who were diagnosed with functional dysphagia (n = 96) based on the Rome IV criteria were analyzed. Age- and sex-adjusted healthy volunteers were also enrolled for comparison. Psychiatric comorbidity and poor sleep quality were defined as total score of 5-item Brief Symptom Rating Scale ≥6 and Pittsburgh Sleep Quality Index ≥6, respectively. RESULTS: The age peak of patients with functional dysphagia was at 40-60 years (47.9%) with females predominant (67%). Forty-four patients (45.8%) had psychiatric comorbidities, whereas 80 (83.3%) experienced poor sleep quality. Female patients were more likely to have trouble falling asleep, shorter sleep duration, and severe bloating. Compared with the healthy volunteers, patients with functional dysphagia had higher 5-item Brief Symptom Rating Scale and Pittsburgh Sleep Quality Index scores (5.34 ± 3.91 vs 1.84 ± 2.61, 9.64 ± 4.13 vs 4.77 ± 3.60, both P < 0.001) but similar results on high-resolution impedance manometry. Those with ineffective esophageal motility (16.7%) had less sleep efficiency than those with normal motility. DISCUSSION: Patients with functional dysphagia were mainly middle-aged women and had a high prevalence of psychiatric comorbidities and sleep disturbances, especially in female patients. Patients with functional dysphagia displayed similar esophageal motility as the healthy volunteers did.

Tissue diagnosis necessary for small endoscopic ultrasound-suspected gastric gastrointestinal stromal tumors 2 cm or less in size: A prospective study focusing on the endoscopic incisional biopsy.

BACKGROUND AND AIM: The small endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs), gastric subepithelial tumors at the muscularis propria layer on EUS, are detected frequently. Bite-on-bite forceps biopsy and EUS-guided tissue sampling yield variable results. This study aimed to analyze clinicopathologic features of the small EUS-suspected gastric GISTs 2 cm or less in size and to evaluate the efficacy and safety of the endoscopic incisional biopsy (EIB) for these small tumors. METHODS: This prospective study investigated 70 patients with small EUS-suspected gastric GISTs 2 cm or less in size in two stages. Firstly, 30 patients were recruited for the efficacy and safety evaluation of the EIB. Secondly, 40 patients were randomly assigned to receive either EIB or the bite-on-bite biopsy for comparison of the diagnostic yield, procedure time, and adverse event rate. RESULTS: Combining two study stages, leiomyoma (74%) was diagnosed histologically to outnumber GIST (26%) with a diagnostic rate of 94% for patients receiving EIB. KIT exon 11 mutations (50%) and PDGFRA exon 12 mutations (16%) were detected in the small gastric GISTs. In the direct comparison, the diagnostic yield of EIB and the bite-on-bite biopsy was 85% and 50%, respectively (P = 0.018). There was no statistically significant difference of the mean procedure time or adverse event rate between these two groups. CONCLUSIONS: Leiomyoma is more common than expected among these small tumors. Tissue diagnosis with an effective and safe sampling technique, such as EIB, is necessary for making further clinical decisions.

Association of Incidence of Acid-related Upper Gastrointestinal Disorders With Glycated Hemoglobin Level.

CONTEXT: Previous cross-sectional studies show diabetes and higher levels of plasma hemoglobin A1c (HbA1c) are associated with a higher prevalence of gastrointestinal (GI) complications. However, whether the glycemic status is associated with incident acid-related upper GI disorders remains unclear. OBJECTIVE: We aimed to determine the effect of hyperglycemia per se, in terms of HbA1c, on the incidence of acid-related disorders. METHODS: We analyzed consecutive subjects who had undergone repeated upper endoscopies as part of the health examinations at the National Taiwan University Hospital from 2005 to 2011. Acid-related endoscopic abnormalities were defined as erosive esophagitis (EE), Barrett's esophagus (BE), and peptic ulcer disease (PUD), which included gastric ulcers (GUs) and duodenal ulcers (DUs). All subjects were categorized by 3 tertiles of HbA1c levels. We analyzed the occurrence of respective acid-related disorders during the follow-up period. RESULTS: A total of 11 391 participants (mean HbA1c level 5.6 ±â€…0.7%) were enrolled in this longitudinal study. During the 38 426.3 person-years of follow-up (mean duration 3.37 ±â€…1.59 years), the incidence of EE, BE, GU, DU, PUD, and any acid-related disorders were 22.1%, 0.5%, 4.5%, 8.6%, 12.3%, and 30.3%, respectively. The higher HbA1c level was associated with higher risk of disease incidents, except BE, during the follow-up (all log-rank P < .001). In the Cox regression analyses with confounding factors fully adjusted, the hazard ratios for EE, GU, DU, PUD, and acid-related disorders were 1.174, 1.339, 1.24, 1.24, and 1.186, respectively, for the third tertile of HbA1c (all P < .05). CONCLUSION: Higher HbA1c level was associated with a higher risk of acid-related upper GI endoscopic abnormalities. Efforts toward better glycemic control may help to prevent the development of late GI complications.

Clinical efficacy and safety of peroral endoscopic myotomy for esophageal achalasia: A multicenter study in Taiwan.

BACKGROUND/OBJECTIVE: Peroral endoscopic myotomy (POEM), a novel minimally invasive treatment for esophageal achalasia, is becoming more popular globally because of its efficacy and safety. We aimed to clarify the technical concerns, efficacy, and safety of POEM for treating esophageal achalasia in Taiwan. METHODS: We conducted a retrospective study on consecutive patients with achalasia who underwent POEM between October 2016 and May 2021 at three medical centers in Taiwan. All patients underwent a comprehensive work-up before POEM, including symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram (TBE), and high-resolution impedance manometry (HRIM), and were re-evaluated three months after POEM. We compared procedure variables, adverse events, and clinical responses, including Eckardt score ≤3 and TBE and HRIM findings. RESULTS: We analyzed 92 patients in total (54 men; mean age 49.5 years [range: 20-87]; type I/II/III/unclassified: 24/51/1/16). The mean POEM procedure duration was 89.5 ± 38.2 min, though it was significantly longer in patients with prior treatment or sigmoid-type achalasia. In total, 91 patients (98.9%) showed immediate technical success, and the overall clinical success rate at three months after POEM was 95.7%. Nearly 60% of patients experienced adverse events during POEM, but most of these were mild and none required further endoscopic or surgical intervention. During a follow-up period of up to five years (median 25 months), only four patients (4.3%) showed symptomatic recurrence, but none required further treatment. CONCLUSION: POEM is a very effective and safe treatment for Taiwanese patients with achalasia, irrespective of their achalasia subtype or prior treatment failure.

Combination of Symptom Profile, Endoscopic Findings, and Esophageal Mucosal Histopathology Helps to Differentiate Achalasia from Refractory Gastroesophageal Reflux Disease.

Achalasia, a rare primary esophageal motility disorder, is often misdiagnosed as refractory gastroesophageal reflux disease (GERD). This study is aimed to identify the clinical and histopathologic features that may help to differentiate these two entities. Patients with untreated achalasia and those with refractory reflux symptoms despite ≥8 weeks of proton-pump inhibitor treatment were enrolled prospectively. All patients underwent validated symptom questionnaires, esophagogastroduodenoscopy with biopsy, and high-resolution impedance manometry (HRIM). Histopathology of esophageal mucosa was compared based on four pre-determined histological criteria: basal cell hyperplasia or papillae elongation, eosinophilic infiltration, petechiae formation, and hypertrophy of the muscularis mucosae (MM). Compared with the GERD patients, patients with achalasia had similar reflux symptoms, but higher Eckardt scores, fewer erosive esophagitis and hiatal hernia, more esophageal food retention on endoscopy, and higher prevalence of hypertrophy of the MM and petechiae formation on histopathology. Multivariate logistic regression based on Eckardt score ≥4, normal esophagogastric junction morphology or esophageal food retention, and coexistence of petechiae formation and hypertrophy of the MM, established the best prediction model for achalasia. Therefore, combination of routinely accessible variables, including Eckardt score, endoscopic features, and histopathology obtained via esophageal mucosal biopsy, may provide an earlier identification of achalasia.

Flexural Behavior of Ultra-High-Performance Fiber-Reinforced Concrete Beams after Exposure to High Temperatures.

Due to the dense structure of ultra-high-performance concrete (UHPC), it is prone to explosive spalling at high temperatures. In this paper, flexural testing of UHPC and high-strength concrete (HSC) beams was carried out at room temperature and after being subjected to different levels of thermal exposure (300-500 °C). The cross-section of the beam specimen was 150 (width) × 200 (depth) mm, and its length was 1500 mm. The flexural and shear design of the beam specimens were carried out in accordance with the ACI 318M-14 code. All of the beams were singly reinforced with two #4 rebars (minimum reinforcement ratio) as a longitudinal tensile reinforcement at the bottom of the specimen and at an effective depth of 165 mm. The flexural load was applied using the three-point load method. The results show that, at room temperature and after being subjected to different thermal exposures, compared with the HSC specimens, the stiffness of the UHPC specimens in the post-cracking stage was relatively larger and the deflection under a given load was smaller. Moreover, whether at room temperature or after exposure to different thermal exposures, the ductility of the UHPC specimens was better than that of the HSC specimens.

A clinically interpretable convolutional neural network for the real-time prediction of early squamous cell cancer of the esophagus: comparing diagnostic performance with a panel of expert European and Asian endoscopists.

BACKGROUND AND AIMS: Intrapapillary capillary loops (IPCLs) are microvascular structures that correlate with the invasion depth of early squamous cell neoplasia and allow accurate prediction of histology. Artificial intelligence may improve human recognition of IPCL patterns and prediction of histology to allow prompt access to endoscopic therapy for early squamous cell neoplasia where appropriate. METHODS: One hundred fifteen patients were recruited at 2 academic Taiwanese hospitals. Magnification endoscopy narrow-band imaging videos of squamous mucosa were labeled as dysplastic or normal according to their histology, and IPCL patterns were classified by consensus of 3 experienced clinicians. A convolutional neural network (CNN) was trained to classify IPCLs, using 67,742 high-quality magnification endoscopy narrow-band images by 5-fold cross validation. Performance measures were calculated to give an average F1 score, accuracy, sensitivity, and specificity. A panel of 5 Asian and 4 European experts predicted the histology of a random selection of 158 images using the Japanese Endoscopic Society IPCL classification; accuracy, sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Expert European Union (EU) and Asian endoscopists attained F1 scores (a measure of binary classification accuracy) of 97.0% and 98%, respectively. Sensitivity and accuracy of the EU and Asian clinicians were 97%, 98% and 96.9%, 97.1%, respectively. The CNN average F1 score was 94%, sensitivity 93.7%, and accuracy 91.7%. Our CNN operates at video rate and generates class activation maps that can be used to visually validate CNN predictions. CONCLUSIONS: We report a clinically interpretable CNN developed to predict histology based on IPCL patterns, in real time, using the largest reported dataset of images for this purpose. Our CNN achieved diagnostic performance comparable with an expert panel of endoscopists.

Endoscopic submucosal dissection comparing with surgical resection in patients with early gastric cancer - A single center experience in Taiwan.

BACKGROUND/PURPOSE: The choice of endoscopic submucosal dissection (ESD) as first line treatment for selected early gastric cancer (EGC) patients was proved as effective as surgical treatment in studies over many countries. Yet there is no such cohort comparison in Taiwan. This study is aimed to describe our experience in ESD treated EGC and to compare the outcomes with those underwent surgical treatment. METHODS: This was a retrospective cohort study reviewing the patients with EGC underwent ESD and surgical treatments in a single tertiary referral center in Taiwan. The primary endpoint was disease specific survival. Recurrence free survival and length of hospital stay were also compared. RESULTS: The disease specific survival between indicated ESD and surgery showed no significant difference (cumulative survival 100% vs. 97.03%, p = 0.39), so as the recurrence free survival (cumulative survival 92.31% vs. 94.06%, p = 0.60). In subgroup analyses of ESD treated patients, a non-significant recurrence rate difference between indicated and non-indicated ESD was found (cumulative recurrence 7.69% vs. 20%, p = 0.39) and a higher recurrence rate in patients with non-R0 resection compared with R0 resection (cumulative recurrence 0% vs. 40%, p < 0.01). However, the shorter duration of hospital stay in ESD group was noted in comparison to surgery (mean 5.67 days vs. 15.75 days, p < 0.01). The ESD patients have minor complications including bleeding, perforation and fever than surgery. CONCLUSION: ESD is a reasonable first line treatment in selected early gastric cancer in additional to surgery. Pre-treatment evaluation and post-ESD review of curability is crucial to further surveillance program or definite therapy including surgery.

Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial.

BACKGROUND: In first-line treatment of Helicobacter pylori, we have previously shown that the eradication frequency was 83·7% (95% CI 80·4-86·6) for triple therapy for 14 days (T14; lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily), 85·9% (82·7-88·6) for concomitant therapy for 10 days (C10; lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily), and 90·4% (87·6-92·6) for bismuth quadruple therapy for 10 days (BQ10; bismuth tripotassium dicitrate 300 mg four times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). In this follow-up study, we assess short-term and long-term effects of these therapies on the gut microbiota, antibiotic resistance, and metabolic parameters. METHODS: This was a multicentre, open-label, randomised trial done at nine medical centres in Taiwan. Adult patients (>20 years) with documented H pylori infection were randomly assigned (1:1:1, with block sizes of six) to receive T14, C10, or BQ10. We assessed long-term outcomes (reinfection frequency, changes in the gut microbiota, antibiotic resistance, and metabolic parameters) in patients with available data, excluding all protocol violators and those with unknown post-treatment H pylori status. Faecal samples were collected before treatment and 2 weeks, 2 months, and at least 1 year after eradication therapy. Amplification of the V3 and V4 hypervariable regions of the 16S rRNA was done followed by high-throughput sequencing. Susceptibility testing for faecal Escherichia coli and Klebsiella pneumoniae was done. This trial is complete and registered with ClinicalTrials.gov, NCT01906879. FINDINGS: Between July 17, 2013, and April 20, 2016, 1620 participants were randomly assigned to the three treatment groups (540 [33%] per group). 1214 (75%) attended 1-year follow-up and are included in this analysis. Compared with baseline, alpha diversity was significantly reduced 2 weeks after T14 (p=0·0002), C10 (p<0·0001), and BQ10 (p<0·0001) treatment. Beta diversity was also significantly altered 2 weeks after T14 (p=0·0010), C10 (p=0·0001), and BQ10 (p=0·0001). Alpha diversity and beta diversity were restored at week 8 (p=0·14 and p=0·918, respectively) and 1 year (p=0·14 and p=0·918) after T14, but were not fully recovered at week 8 and after 1 year in patients treated with C10 (p=0·0001 and p=0·013 at week 8; p=0·019 and p=0·064 at 1 year) and BQ10 (p<0·0001 and p=0·0002; p=0·001 and p=0·029). A transient increase at week 2 after T14 and C10 of the resistance rates of E coli to ampicillin-sulbactam (12% [15/127] to 66% [38/58] for T14, 7% [10/135] to 64% [28/44] for C10), cefazolin (13% [16/127] to 43% [25/58] for T14, 10% [13/135] to 41% [18/44] for C10), cefmetazole (8% [10/127] to 26% [15/58] for T14, 4% [5/135] to 18% [8/44] for C10), levofloxacin (8% [10/127] to 35% [20/58] for T14, 7% [10/135] to 32% [14/44] for C10), gentamicin (13% [19/146] to 47% [27/58] for T14, 15% [22/149] to 45% [20/44] for C10), and trimethoprim-sulfamethoxazole (33% [48/146] to 86% [50/58] for T14, 28% [42/148] to 86% [38/44] for C10; p<0·05 in paired samples in the above analyses) returned to basal state at week 8 and after 1 year. Although bodyweight and body-mass index slightly increased, there were significant improvements in metabolic parameters, with a decrease in insulin resistance, triglycerides, and LDL and an increase in HDL. Overall, there was no significant change in the prevalence of metabolic syndrome at week 8 and 1 year after T14, C10, and BQ10. INTERPRETATION: Eradication of H pylori infection has minimal disruption of the microbiota, no effect on antibiotic resistance of E coli, and some positive effects on metabolic parameters. Collectively, these results lend support to the long-term safety of H pylori eradication therapy. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.