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.

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.

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 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.

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.

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.

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.

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.

Patient-controlled analgesia for background pain of major burn injury.

BACKGROUND: Studies have suggested that intravenous patient-controlled analgesia (IV-PCA) can be used safely for the treatment of background pain in burn patients. However, no comprehensive protocols have been published. How patient or surgical factors correlate with the amount of opioid consumption remains unclear. The aim of this study is to provide an IV-PCA protocol for alleviating pain for burn injuries, and to assess factors correlated with opioid consumption. METHODS: At the Mackay Memorial Hospital, a retrospective analysis from June 27th to October 31st of 2015 was carried out to investigate the use of IV-PCA in relation to the demographic and clinical data of patients who suffered from burn injuries due to a massive explosion of flammable powder. A standardized morphine IV-PCA protocol with rapid escalation was implemented. Variables assessed included age, weight, gender, days of usage, total surface area burned (TBSAB) and operations. RESULTS: Among the 23 patients who received IV-PCA for burn pain control, it was noted that the larger the TBSAB and the higher the visual analogue scale (VAS), the more amount of morphine was consumed. Correlations between morphine consumption positively with weight (P < 0.01), female gender (P < 0.01), severity of injury (P = 0.01), and negatively with receiving operations (P = 0.01) were statistically significant. CONCLUSION: As the daily morphine consumption was positively correlated with TBSAB, VAS, weight, female gender, the use of our IV-PCA protocol was sufficient in the management of background pain for patients with major burn injury.

Early timing of single balloon enteroscopy is associated with increased diagnostic yield in patients with overt small bowel bleeding.

BACKGROUND/PURPOSE: Although performing balloon enteroscopy soon after the onset of small bowel bleeding appeared to enhance diagnostic rate, the optimal timing was unclear. METHODS: A retrospective cohort study in a single referral center. Patients with overt, suspected small bowel bleeding who underwent primary single-balloon enteroscopy (SBE) were evaluated to determine the association between procedure timing and diagnostic yield rates. RESULTS: A total of 220 patients were enrolled (47.7% males; mean age, 65.6 ± 18.1 years). They were stratified into four groups based on the timing of SBE: emergency (<24 h after onset or continued bleeding, n = 64), 24-72 h (n = 28), 3-7 days (n = 41), and >7 days (n = 87). A significant trend of decreasing diagnostic yields was observed across the groups (90.6%, 67.9%, 68.3%, and 44.8%, respectively, P < 0.0001). Diagnostic yield rates were different between emergency and 24-72 h groups (P < 0.0001), and between 3 and 7 days and >7 days groups (P < 0.05), but not between 24 and 72 h and 3-7 days groups (P = 0.97). In multivariate regression analysis, emergency, ≤ 3 days, and ≤7 days SBEs had greater yield rates than SBEs at later timings. CONCLUSION: The likelihood of diagnostic yield was highest when SBE was performed during continued bleeding or within 24 h of onset, and gradually declined as waiting time increased. We therefore recommend that SBE should be performed as soon as possible, preferably no later than seven days.

Etiologies and clinical characteristics of non-obstructive dysphagia in a Taiwanese population: A prospective study based on high-resolution impedance manometry.

BACKGROUND: Esophageal motility disorders are the major cause of non-obstructive dysphagia (NOD), but may be underdiagnosed. In this high-resolution impedance manometry (HRIM)-based study, we aimed to clarify the etiologies and clinical characteristics of patients presenting with NOD in a Taiwanese population. METHODS: From October 2014 to July 2017, consecutive patients with the chief complaint of dysphagia were prospectively enrolled in the study at a tertiary medical center. All subjects underwent a comprehensive diagnostic work-up, which included validated symptom questionnaires, esophagogastroduodenoscopy, timed barium esophagogram, and HRIM. Those with obstructive esophageal lesions were excluded. Esophageal motility disorders were diagnosed using the updated Chicago Classification v3.0. We categorized all patients based on the HRIM results, and compared the clinical characteristics and parameters between groups. RESULTS: A total of 120 patients (55 men; mean age [range], 52 [13-87] years) were analyzed. Achalasia was the most common diagnosis by HRIM (n = 66, 55%), followed by ineffective esophageal motility (n = 15, 12.5%), and absent contractility (n = 6, 5%). Patients with achalasia experienced increased vomiting (62.1% vs. 31.5%, p = 0.001), significant weight loss (22.7% vs. 7.4%, p = 0.025), delayed esophageal emptying (90.9% vs. 12.9%, p < 0.001), and abnormal bolus transit (100% vs. 25.9%, p < 0.001) compared with non-achalasia patients. CONCLUSION: Based on HRIM and the updated Chicago Classification, achalasia was the most common diagnosis of NOD in a Taiwanese population. HRIM allows for a more detailed assessment and may assist in the tailoring of further treatment plans.

Systematic Review with Meta-Analysis: Concomitant Therapy vs. Triple Therapy for the First-Line Treatment of Helicobacter pylori Infection.

BACKGROUND: Whether concomitant therapy is superior to triple therapy of various treatment lengths for the first-line treatment of H. pylori remains controversial. The objective of this study is to compare the efficacy of concomitant therapy and triple therapy given for 5-14 days. METHODS: Randomized control trials (RCTs) comparing the efficacy of concomitant therapy for 5-14 days and proton pump inhibitor-amoxicillin-clarithromycin (PAC)-based triple therapy for 5-14 days in the first-line treatment of adult patients with H. pylori infection published from 1990 to January 2018 were searched from the PubMed, Cochrane Library, and Embase. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and the adverse effects, respectively. Subgroup analyses were also performed according to treatment length. This study is registered with PROSPERO, number CRD42017081328. RESULTS: Of the 639 articles identified, 23 RCTs including 3305 patients in the concomitant therapy group and 3327 patients in the triple therapy group were eligible. Overall, concomitant therapy was superior to triple therapy [risk ratio (RR): 1.15; 95% confidence interval (CI): 1.09-1.21; p < 0.001]. However, there were significant heterogeneity (I2 = 74.0%, p < 0.001). In the subgroup analysis, 5-day concomitant therapy was superior to 5-day triple therapy (RR: 1.30; 95% CI: 1.04-1.62; p = 0.02), 5- or 7-day concomitant therapy was superior to 7-day triple therapy (RR: 1.16; 95% CI: 1.12-1.21; p < 0.001), and 5- or 7-, or 10- or 14-day concomitant therapy was superior to 10-day triple therapy (RR: 1.15; 95% CI: 1.08-1.23; p < 0.001). However, 5- or 10-day concomitant therapy was not superior to 14-day triple therapy (RR: 1.02; 95% CI: 0.89-1.16; p = 0.796). The frequency of adverse effects was significantly higher in concomitant therapy than triple therapy (RR: 1.19; 95% CI: 1.06-1.34; P = 0.004). CONCLUSIONS: Concomitant therapy given for 5 or 10 days was superior to 5- or 7-, or 10-day PAC-based triple therapy, but was not superior to 14-day triple therapy.

Increased Pancreatic Echogenicity with US: Relationship to Glycemic Progression and Incident Diabetes.

Purpose To evaluate the association between increased pancreatic echogenicity (IPE) and the risk of glycemic progression and incident diabetes. Materials and Methods This retrospective study was approved by the institutional review board, with waiver of informed consent. Consecutive individuals who had undergone abdominal ultrasonography as part of a health examination at a tertiary hospital between January 2005 and December 2011 were included. IPE was defined as increased echogenicity of the pancreas compared with that of the left lobe of liver. Glycemic progression was defined as the development of new prediabetes or diabetes in normoglycemic participants or as new diabetes in prediabetic participants during the follow-up period (median, 3.17 years; interquartile range, 2.01-4.67 years). The occurrence of incident diabetes, defined as a new diagnosis of diabetes during follow-up, was also analyzed. Results Mean age of the 32 346 participants was 50.4 years ± 12.2, and 48% (15 489 of 32 346) were female. The prevalence of IPE and nonalcoholic fatty liver disease (NAFLD) was 8.4% (2720 of 32 346) and 41.4% (13 389 of 32 346), respectively. A total of 8856 participants were included in the follow-up analysis. During the 29 819.2 person-years of follow-up, 1217 (13.7%) and 449 (5.1%) of the 8856 participants developed glycemic progression and new diabetes, respectively. IPE was associated with more glycemic progression (hazard ratio, 1.54; 95% confidence interval: 1.23, 1.92; P < .001) and incident diabetes (hazard ratio, 1.49; 95% confidence interval: 1.05, 2.11; P = .024) after adjustment for confounders, HbA1c concentration, and NAFLD. Conclusion Increased pancreatic echogenicity is associated with deteriorating glycemic parameters and higher risk of glycemic progression and incident diabetes, independent of HbA1c concentration and NAFLD. © RSNA, 2018 Online supplemental material is available for this article.

Lessons from pathological analysis of recurrent early esophageal squamous cell neoplasia after complete endoscopic radiofrequency ablation.

BACKGROUND: Endoscopic radiofrequency ablation (RFA) is a treatment option for early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up studies are lacking. The risks of local recurrence and "buried cancer" are also uncertain. METHODS: Patients with flat-type ESCN who were treated with balloon-type ± focal-type RFA were consecutively enrolled. Follow-up endoscopy was performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic resection was performed for persistent and recurrent ESCN, and the histopathology of resected specimens was assessed. RESULTS: A total of 35 patients were treated with RFA, of whom 30 (86 %) achieved a complete response, three were lost to follow-up, and five (14 %) developed post-RFA stenosis. Two patients had persistent ESCN and received further endoscopic resection, in which the resected specimens all revealed superficial submucosal invasive cancer. Six of the 30 patients with successful RFA (20 %) developed a total of seven episodes of local recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all of which were successfully resected endoscopically without adverse events. Histological analysis of the resected specimens revealed that six (86 %) had esophageal glandular ductal involvement, all of which extended deeper than the muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67 suggested a clonal relationship between the ductal involvement and epithelial cells. None of the tumors extended out of the ductal structure; no cases of cancer buried beneath the normal neosquamous epithelium were found. CONCLUSIONS: Because ductal involvement is not uncommon and may be related to recurrence, the use of RFA should be conservative and may not be the preferred primary treatment for early ESCN.

Muscular thickness of lower esophageal sphincter and therapeutic outcomes in achalasia: A prospective study using high-frequency endoscopic ultrasound.

BACKGROUND AND AIM: Patients with achalasia typically have thicker lower esophageal sphincter muscles, which can affect the distensibility of the esophagogastric junction. We aimed to assess whether these muscular features, measured using high-frequency endoscopic ultrasound, affect treatment outcomes. METHODS: Consecutive adult patients with suspected achalasia were enrolled prospectively. They underwent a comprehensive diagnostic workup, including endoscopic ultrasound. The thickness of the lower esophageal sphincter, including the internal circular and outer longitudinal muscles, was measured using a 12-MHz ultrasonic miniprobe. Follow-up was performed at 1 month and then at 6-month intervals, after treatment. Treatment response was defined as a reduction in Eckardt score to ≤3 or an improvement in the height of the timed barium esophagogram of ≥50%. RESULTS: Of the 29 patients who received pneumatic dilatation, all but one (96.6%) exhibited a good short-term treatment response. At an average follow-up time of 18.5 (12-55.5) months, patients who had a mid-term recurrence after pneumatic dilatation had a significantly thicker outer longitudinal muscle (1.8 [1.5-1.8] vs 0.9 [0.8-1.7] mm, P = 0.036), but not internal circular muscle (2.0 [1.9-2.5] vs 2.1 [1.2-2.7] mm, P = 0.874) or total lower esophageal sphincter (3.7 [3.5-4.4] vs 3.6 [2.0-4.1] mm, P = 0.362). Patients with an outer longitudinal muscle ≥1.3 mm thick had a significantly lower mid-term remission rate than others (36.3% vs 100%, P = 0.01). CONCLUSION: Thickening of the outer longitudinal muscle at the lower esophageal sphincter is associated with poor mid-term treatment outcomes for achalasia patients treated with pneumatic dilatation.

A training program of a new simplified classification of magnified narrow band imaging for superficial esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS: A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS: The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P < 0.05). CONCLUSIONS: A well-designed training program can improve the diagnostic accuracy in evaluating cancer invasion depth, with substantial agreement.

Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial.

BACKGROUND: Whether concomitant therapy is superior to bismuth quadruple therapy or 14-day triple therapy for the first-line treatment of Helicobacter pylori infection remains poorly understood. We aimed to compare the efficacy and safety of 10-day concomitant therapy, 10-day bismuth quadruple therapy, and 14-day triple therapy in the first-line treatment of H pylori. METHODS: In this multicentre, open-label, randomised trial, we recruited adult patients (aged >20 years) with H pylori infection from nine medical centres in Taiwan. Patients who had at least two positive tests from the rapid urease test, histology, culture, or serology or who had a single positive 13C-urea breath test for gastric cancer screening were eligible for enrolment. Patients were randomly assigned (1:1:1) to either concomitant therapy (lansoprazole 30 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg, all given twice daily) for 10 days; bismuth quadruple therapy (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) for 10 days; or triple therapy (lansoprazole 30 mg, amoxicillin 1 g, and clarithromycin 500 mg, all given twice daily) for 14 days. A computer-generated permuted block randomisation sequence with a block size of 6 was used for randomisation, and the sequence was concealed in an opaque envelope until the intervention was assigned. Investigators were masked to treatment allocation. The primary outcome was the eradication frequency of H pylori with first-line therapy assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01906879. FINDINGS: Between July 17, 2013, and April 20, 2016, 5454 patients were screened for eligibility. Of these, 1620 patients were randomly assigned in this study. The eradication frequencies were 90·4% (488/540 [95% CI 87·6-92·6]) for 10-day bismuth quadruple therapy, 85·9% (464/540 [82·7-88·6]) for 10-day concomitant therapy, and 83·7% (452/540 [80·4-86·6]) for 14-day triple therapy in the intention-to-treat analysis. 10-day bismuth quadruple therapy was superior to 14-day triple therapy (difference 6·7% [95% CI 2·7-10·7, p=0·001), but not 10-day concomitant therapy. 10-day concomitant therapy was not superior to 14-day triple therapy. The frequency of adverse events was 67% (358/533) in patients treated with 10-day bismuth quadruple therapy, 58% (309/535) in patients treated with 10-day concomitant therapy, and 47% (252/535) in patients treated with 14-day triple therapy. INTERPRETATION: Bismuth quadruple therapy is preferable to 14-day triple therapy in the first-line treatment in the face of rising prevalence of clarithromycin resistance. Concomitant therapy given for 10 days might not be optimum and a longer treatment length should be considered. FUNDING: National Taiwan University Hospital and Ministry of Science and Technology of Taiwan.