Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C/D Esophagitis: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. METHODS: A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. RESULTS: Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. DISCUSSION: Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Ineffective esophageal motility in Chicago Classification version 4.0 better predicts abnormal acid exposure.

BACKGROUND: The updated Chicago Classification version 4.0 (CCv4.0) establishes a more stringent criteria to diagnose ineffective esophageal motility (IEM). This study aims to investigate the clinical significance of IEM in CCv4.0 in the context of gastroesophageal reflux disease (GERD). METHODS: A retrospective study was conducted among suspected GERD patients who had heartburn and/or regurgitation as their chief complaints and completed esophageal function tests in our center from 2017 to 2019. Patients were further grouped as "CCv3.0 IEM" and normal motility according to Chicago Classification version 3.0 (CCv3.0), and as "CCv4.0 IEM" and normal motility according to CCv4.0. The clinical characteristics, high-resolution manometry, esophageal reflux monitoring, and proton pump inhibitor (PPI) efficacy were compared between different groups. Multivariate analyses were performed to identify esophageal motility parameters associated with reflux burden and symptom outcome. RESULTS: Of 172 subjects included, 93 patients were identified as CCv3.0 IEM, 69 as CCv4.0 IEM. IEM in either version was concomitant with elevated acid burden and impaired esophageal clearance as compared to normal motility in corresponding diagnostic criteria, while the only presence of IEM in CCv4.0 was predictive to abnormal acid exposure (AET > 6%: OR = 2.66, 95% CI [1.27-5.56], p < 0.01). The presence of "CCv3.0 IEM" and low EGJ-CI (EGJ-CI < 39.1 mmHg·cm) had no added value in predicting increased reflux burden. No interaction effect was found between the presence of IEM and a weakened EGJ. None of the manometric variables was capable of predicting PPI response. CONCLUSIONS: Stringent criteria of IEM in CCv4.0 can better predict abnormal acid exposure as compared to CCv3.0.

Impact of the coronavirus disease 2019 pandemic on irritable bowel syndrome.

BACKGROUND AND AIM: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. METHODS: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. RESULTS: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. CONCLUSION: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

Novel physiologic nomogram discriminates symptom outcome in patients with erosive esophagitis.

BACKGROUND AND AIM: Most of patients with erosive esophagitis (EE) are of LA grade A&B with low reflux burden, therefore require further esophageal function tests (EFTs). One-third of them respond poorly to pump proton inhibitor (PPI) treatment. The aim was to establish and validate a physiologic nomogram to discriminate symptom outcome to PPI treatment in patients with EE. METHODS: A total of 79 EE patients with heartburn who underwent EFTs and received PPI therapy were randomly assigned into a training set (n = 55) and a validation set (n = 24). Clinical data including physiologic parameters from EFTs were collected. Significant factors for the positive symptomatic outcome were identified using logistic regression analysis. Physiologic signature was developed using the least absolute shrinkage and selection operator algorithm. The nomogram was established by combining significant factors and physiologic signature, and its performance was evaluated and validated in the training and validation set. The clinical value of the nomogram was measured by decision curve analysis. RESULTS: Significant factors for positive symptomatic response to PPI treatment were identified as follows: acid exposure time, total number of reflux episodes, and two novel metrics including mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index. The nomogram which incorporated both significant factors and physiologic signature demonstrated good performance in the training and validation sets [C-index: 0.938 (95% CI 0.882-0.995); 0.839 (95% CI 0.678-0.995), respectively]. Decision curves showed significant clinical usefulness. CONCLUSION: The first physiologic nomogram was developed to discriminate the individualized response to PPI therapy among EE patients.

A study of proximal esophageal baseline impedance in identifying and predicting laryngopharyngeal reflux.

BACKGROUND AND AIM: Laryngopharyngeal reflux (LPR) is caused by the reflux of gastric contents beyond the esophagus into the larynx and pharynx. However, upper esophageal sphincter (UES) motility and proximal esophagus reflux parameters are poorly studied. This study aims to explore the characteristics of UES motility and reflux parameter among LPR patients. METHODS: Patients with laryngopharyngeal symptoms only (L), patients with laryngopharyngeal symptoms and typical esophageal symptoms (L + E), patients with typical esophageal symptoms only (E), and healthy controls (H) were retrospectively included. Physiological profiles were studied and compared among groups using both high-resolution manometry and pH-impedance monitoring, including UES basal pressure, residual pressure, relaxation duration time, recovery time, the time to nadir pressure, UES length, proximal contractile integral, and proximal mean nocturnal baseline impedance (MNBI). Patients' symptom outcomes were also analyzed. RESULTS: A total of 242 patients were included. Proximal MNBI was significantly lower in patients with both laryngopharyngeal and esophageal symptoms (17 cm above low esophageal sphincter [LES]: L vs L + E vs E vs H = 3689.7 vs 2500.0 vs 3073.0 vs 3996.0; 15 cm above LES: L vs L + E vs E vs H = 3155.9 vs 2553.4 vs 3198.9 vs 2985.2; P < 0.001). Patients responded to proton pump inhibitor treatment also had lower proximal MNBI than those who did not (17 cm above LES: 1834.0 vs 3500.0; 15 cm above LES: 1946.5 vs 3432.6; P < 0.001). CONCLUSION: Decreased proximal MNBI can not only identify LPR patients but also predict patients' symptom outcomes.

Herbal medicine in the treatment of functional gastrointestinal disorders: A systematic review with meta-analysis.

BACKGROUND AND AIMS: The efficacy of herbal medicines (HMs) for functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional dyspepsia (FD) and functional constipation (FC) is controversial. A systematic review with meta-analysis was conducted to determine their effectiveness for FGIDs. METHODS: We searched the following electronic databases till July 2019 with English language restriction: The Cochrane Library, EMBASE and PUBMED. Randomized double-blind controlled trials of HMs compared with placebo or conventional pharmacological drugs for adult FGIDs patients were included. RESULTS: In total, 49 trials involving 7396 participants with FGIDs were included. The risk of bias was low in 9, unclear in 36, and high in 4 trials. More than 33 different herbal formulae were tested. HMs demonstrated statistically significant benefits for symptom improvement compared with placebo in 46 trials (RR = 1.67, 95% CI 1.48-1.88). When compared with conventional pharmacological therapy in 5 trials, HMs were found to be non-inferior (RR = 1.10, 95% CI 1.03-1.18). The number of trials with regards to FD, IBS and FC were 19, 23 and 7 respectively. Subgroup analysis found that HMs were better than placebo in alleviating symptoms for FD (RR = 1.50, 95% CI 1.32-1.69), IBS (RR = 1.62, 95% CI 1.32-1.97) and FC (RR = 3.83, 95% CI 2.26-6.50). HMs tended to have more patients with adverse events than placebo, but similar to conventional pharmacological drugs. CONCLUSIONS: Our findings provide a positive signal for HMs as a potentially well-tolerated and effective treatment for FGIDs, deserving further examination in high-quality trials.

The Disease Spectrum and Natural History of Patients With Abdominal Bloating or Distension: A Longitudinal Study.

Background/Aims: Abdominal bloating or distension (AB/D) is a common complaint in the outpatient of gastroenterology department. Since the potential contributors are numerous and complex, a longitudinal study on the disease spectrum and natural history of patients was performed to better understand the key factors of AB/D. Methods: Consecutive patients with the chief complaint of AB/D referred to the outpatient clinic were screened. Functional gastrointestinal disorders (FGIDs) were diagnosed according to Rome IV criteria. A 3-year follow-up was performed to seek for the changes in symptoms as well as disease spectrum. Results: A total of 261 participants were enrolled and 139 completed the follow-up. Most patients suffered from moderate to severe symptoms more than 1 day per week. Common causes of AB/D were FGIDs (51.7%) and organic diseases (17.2%). The latter group was older with lower body mass index (BMI). Functional dyspepsia was the most common type of FGIDs in AB/D. The symptoms of 18.0% of participants failed to improve at the end of the 3-year follow-up, and those diagnosed with FGIDs were most likely to continue to suffer. Abdominal pain was a positive predictive factor for good prognosis in the FGIDs group. Besides, only 22.7% of participants had a consistent diagnosis of FGIDs during follow-up. Conclusions: FGIDs are the most common diagnosis in patients with AB/D. Symptoms were especially hard to be improved. Classification diagnoses of FGIDs in AB/D patients fluctuated significantly over time.

Development and Validation of Serum Markers as Noninvasive Diagnostic Methods for Achalasia.

INTRODUCTION: Currently, the diagnosis of achalasia mainly relies on invasive or radioactive examinations. This study aimed to develop a noninvasive diagnostic method for achalasia based on specific serum markers. METHODS: Serum levels of profilin-1, galectin-10, immunoglobulin heavy variable 3-9, vasodilator-stimulated phosphoprotein, and transgelin-2 were measured in patients with achalasia and controls by enzyme-linked immunosorbent assay. The diagnostic values and thresholds were determined by the receiver operating characteristic curve analysis. Then, patients with dysphagia were prospectively enrolled to validate the ability of these molecules for achalasia diagnosing. RESULTS: A total of 142 patients with achalasia and 50 nonachalasia controls (healthy volunteers and patients with reflux esophagitis) were retrospectively included. The serum levels of profilin-1, galectin-10, and transgelin-2 in patients with achalasia were significantly higher than those in healthy volunteers and patients with reflux esophagitis ( P all < 0.001). Profilin-1, galectin-10, and transgelin-2 were of good performance in diagnosing achalasia, with optimal thresholds of 2,171.2, 33.9, and 1,630.6 pg/mL, respectively. Second, 40 patients with dysphagia were prospectively enrolled to the validation of achalasia. For profilin-1, the positive predictive value, negative predictive value, sensitivity, and specificity were 100.0%, 64.5%, 45.0%, and 100.0%, respectively. The figures for transgelin-2 were 65.5%, 90.9%, 95.0%, and 50.0%. When both increased, the positive predictive value reached to 100.0%. When both indexes were normal, the negative predictive value was 100.0%. DISCUSSION: Profilin-1 and transgelin-2 were promising biomarkers for achalasia diagnosis and performed better in combination. Further multicenter studies are necessary to verify their application as preliminary screening tools for achalasia.

Current complementary and alternative therapy forgastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a widely prevalent gastrointestinal disorder, affecting ∼13.3% of the global population. There are shortages and limitations of current GERD treatment modalities, and complementary and alternative therapy (CAT) is a promising option to fill in the gap. Dietary and lifestyle modifications might play an important and complementary role in alleviating GERD symptoms. Traditional Chinese medicine and brain-gut behavior therapy, particularly transcutaneous electrical acustimulation and diaphragmatic breathing therapy were shown to be useful adjuncts or alternatives in treating GERD. CAT may help to relieve GERD symptoms, minimize medication dosage, and slow the demand for surgery. The aim of this review was to summarize the existing evidence of some common CATs in treating symptomatic GERD, including dietary modification, lifestyle change, traditional Chinese medicine, and brain-gut behavior therapy.

Clinical relevance of salivary pepsin detection in diagnosing gastroesophageal reflux disease subtypes.

Background: Gastroesophageal reflux disease (GERD) is heterogeneous with a varied symptom spectrum and reflux profiles. Its definite diagnosis often requires invasive tools including endoscopy or reflux monitoring. The aim of this study was to investigate the clinical relevance of salivary pepsin detection as a non-invasive screening tool to diagnose GERD of different subtypes. Methods: A total of 77 patients with suspected GERD symptoms and 12 asymptomatic controls were analysed. All participants performed symptom evaluation, upper endoscopy, esophageal manometry, and 24-hour multichannel intraluminal impedance-dual pH probe monitoring. Saliva was self-collected across three different time points: at early fasting, postprandially, and at symptom occurrence. Salivary pepsin levels were measured via Peptest. The optimal threshold of salivary pepsin for diagnosing distal or proximal reflux was determined according to a receiver-operating characteristic curve. Results: The average salivary pepsin concentration of suspected GERD patients was significantly higher than that of controls (100.63 [68.46, 141.38] vs 67.90 [31.60, 115.06] ng/mL, P = 0.044), although no difference was found among patients with different symptom spectrums. The distal reflux group had a higher average pepsin concentration than non-reflux patients (170.54 [106.31, 262.76] vs 91.13 [63.35, 127.63] ng/mL, P = 0.043), while no difference was observed between the distal reflux group and the proximal reflux group. The optimal cut-off value of salivary pepsin concentration for diagnosing pathological distal reflux was 157.10 ng/mL, which was higher than that for diagnosing pathological proximal reflux (122.65 ng/mL). The salivary pepsin concentration was significantly correlated with distal and proximal reflux parameters. Conclusions: Salivary pepsin measurement can help in identifying true GERD with pathological distal reflux or proximal reflux, regardless of different symptom spectrums. A higher threshold should be applied for diagnosing distal reflux than for proximal reflux.

Achalasia: The Current Clinical Dilemma and Possible Pathogenesis.

Achalasia is a primary esophageal motility disorder manifested by dysphagia and chest pain that impair patients' quality of life, and it also leads to chronic esophageal inflammation by food retention and increases the risk of esophageal cancer. Although achalasia has long been reported, the epidemiology, diagnosis and treatment of achalasia are not fully understood. The current clinical dilemma of achalasia is mainly due to its unclear pathogenesis. In this paper, epidemiology, diagnosis treatment, as well as possible pathogenesis of achalasia will be reviewed and summarized. The proposed hypothesis on the pathogenesis of achalasia is that genetically susceptible populations potentially have a higher risk of infection with viruses, triggering autoimmune and inflammation responses to inhibitory neurons in lower esophageal sphincter.

The molecular pathogenesis of achalasia: a paired lower esophageal sphincter muscle and serum 4D label-free proteomic study.

Background: Achalasia is a primary esophageal motility disorder with potential molecular pathogenesis remaining uncertain. This study aimed to identify the differentially expressed proteins and potential pathways among achalasia subtypes and controls to further reveal the molecular pathogenesis of achalasia. Methods: Paired lower esophageal sphincter (LES) muscle and serum samples from 24 achalasia patients were collected. We also collected 10 normal serum samples from healthy controls and 10 normal LES muscle samples from esophageal cancer patients. The 4D label-free proteomic analysis was performed to identify the potential proteins and pathways involved in achalasia. Results: Analysis of Similarities showed distinct proteomic patterns of serum and muscle samples between achalasia patients and controls (both P < 0.05). Functional enrichment analysis suggested that these differentially expressed proteins were immunity-, infection-, inflammation-, and neurodegeneration-associated. The mfuzz analysis in LES specimens showed that proteins involved in the extracellular matrix-receptor interaction increased sequentially between the control group, type III, type II, and type I achalasia. Only 26 proteins altered in the same directions in serum and muscle samples. Conclusions: This first 4D label-free proteomic study of achalasia indicated that there were specific protein alterations in both the serum and muscle of achalasia, involving immunity, inflammation, infection, and neurodegeneration pathways. Distinct protein clusters between types I, II, and III revealed the potential molecular pathways associated with different disease stages. Analysis of proteins changed in both muscle and serum samples highlighted the importance of further studies on LES muscle and revealed potential autoantibodies.

Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Clinical outcomes of asymptomatic low-grade esophagitis: results from a multicenter Chinese cohort.

Background: Asymptomatic low-grade (Los Angeles Classification Grades A and B) esophagitis is common in clinical practice with unclear clinical outcomes. This study aimed to explore the clinical outcomes of asymptomatic low-grade esophagitis. Methods: This was a multicenter cohort study conducted by three academic hospitals in China. Asymptomatic low-grade esophagitis patients between January 2015 and December 2019 were included. Mucosal healing condition 1 year after initial diagnosis, symptom outcomes, and proton-pump inhibitor (PPI) use within 1 year after initial diagnosis were studied and compared. Results: A total of 248 asymptomatic low-grade esophagitis patients were included. Esophagitis disappeared in 76.2% of patients 1 year after initial diagnosis. In terms of symptom outcomes, 89.9% of patients did not present gastroesophageal reflux disease (GERD) symptoms within 1 year after initial diagnosis. No significant difference was found in the proportion of patients who presented GERD symptoms and in the proportion of patients with persistent esophagitis between the PPI group and the non-PPI group (all P > 0.05). Patients with initial Grade B esophagitis were more likely to present follow-up GERD symptoms (16.0% vs 7.5%, P = 0.041) and had more severe follow-up esophagitis than those with Grade A (P < 0.001). Patients with follow-up GERD symptoms were more likely to have persistent esophagitis than those without. Conclusions: This study demonstrated that asymptomatic low-grade esophagitis had relatively benign clinical outcomes. Patients with initial Grade B esophagitis and patients with follow-up GERD symptoms were more likely to be those who are in genuine need of further follow-up and treatments.

Acid Exposure Time > 6% Might Not Improve the Therapeutic Outcome in Chinese Gastroesophageal Reflux Disease Patients.

BACKGROUND/AIMS: There is less acid burden in Chinese gastroesophageal reflux disease (GERD) patients. However, the Lyon consensus proposed a higher threshold of acid exposure time (AET > 6%) for GERD. The aims are to apply the updated criteria in Chinese GERD patients and clarify its influence on clinical outcome. METHODS: Patients who were referred for both esophageal high-resolution manometry and 24-hour esophageal pH monitoring due to reflux symptoms were retrospectively screened. Those patients with AET > 4% was included and grouped into either AET 4-6% or AET > 6%. Their manometric profile, reflux profile, and response to proton pump inhibitors (PPIs) were evaluated. Adjunctive evidence proposed in the Lyon consensus was added in patients with AET 4-6% for therapeutic gain. Another group of patients (n = 144) with AET < 4% were included as non-GERD patients. RESULTS: In total, 151 patients (102 males) were included with 113 patients AET > 6% (74.9%). GERD patients with AET > 4% were with more male, older patients, and higher body mass index compared with non-GERD patients. Meanwhile, GERD patients were less competent in esophagogastric junction pressure. However, the manometric and reflux profile were similar between patients with AET > 6% and 4-6%. The response rate of PPI therapy was 64.6% and 63.2%, respectively, in groups of AET > 6% and 4-6% (P > 0.05). When adjunctive evidence was added in patients with AET 4-6%, no therapeutic gain was obtained. CONCLUSIONS: The efficacy of PPI therapy was similar in patients with AET > 6% and 4-6%. The increase of the AET threshold did not influence the clinical outcome of Chinese GERD patients.

Upright Integrated Relaxation Pressure Predicts Symptom Outcome for Esophagogastric Junction Outflow Obstruction.

BACKGROUND/AIMS: Esophagogastric junction outflow obstruction (EGJOO) is characterized by elevated integrated relaxation pressure (IRP) and preserved esophageal peristalsis. The clinical significance of EGJOO is uncertain. This study aim to describe the clinical characteristics of these patients and to find out potential parameters to predict patients' symptom outcome. METHODS: Consecutive patients who received high-resolution manometry examination in our hospital in 2013-2019 and met the diagnostic criteria of EGJOO were retrospectively included. Motility and reflux parameters as well as endoscopy and barium esophagogram results were studied and compared. Patients were also followed up to record their treatment methods and symptom outcomes. RESULTS: A total of 138 EGJOO (accounting for 5.2% of total patients taking high-resolution manometry examination in our hospital) patients were included. Only 2.9% of these patients had persistent dysphagia. A total of 81.8% of EGJOO patients had symptom resolution during follow-up. Patients with persistent dysphagia had significantly higher upright IRP (16.6 [10.3, 19.8] vs 7.8 [3.2, 11.5]; P = 0.026) than those without. Upright IRP can effectively distinguished patients with persistent dysphagia (area under curve: 0.826; P = 0.026) using optimal cut-off value of 9.05 mmHg. CONCLUSION: EGJOO patients with persistent dysphagia and higher upright IRP (median > 9.05 mmHg) needs further evaluation and aggressive management.

The Number of Interstitial Cells of Cajal Differs Among Different Subtypes of Achalasia and is Related to Patients' Prognosis.

INTRODUCTION: Achalasia is a primary esophageal motility disorder with heterogeneous manometric subtypes and prognosis, characterized by degeneration of the esophageal myenteric plexus, and reduction in interstitial cells of Cajal (ICCs). This study aimed to explore the histopathologic characteristics of lower esophageal sphincter (LES) muscle from patients with achalasia with different subtypes and different prognosis. METHODS: We examined specimens of LES muscle from 122 patients with achalasia who underwent peroral endoscopic myotomy and from 10 control patients who underwent esophagectomy for esophageal cancer. Hematoxylin-eosin staining was performed to assess inflammation infiltration, fibrosis, and atrophy. Specific immunohistochemical staining was performed to identify ICCs and neuronal nitric oxide synthase (nNOS). RESULTS: The number of ICCs in patients with type I achalasia was significantly lower than that in patients with type II achalasia, followed by that in control patients (type I vs type II vs control group= 0.4 vs 1.2 vs 9.5; P < 0.001). The number of nNOS-positive cells was significantly lower in patients with achalasia than that in control patients (type I vs type II vs control group = 0.0 vs 0.0 vs 8.0; P < 0.001). Nonrecurrent group had significantly more ICCs than recurrent group (type I: nonrecurrent vs recurrent = 1.0 vs 0.1; P = 0.010; type II: nonrecurrent vs recurrent = 2.0 vs 0.4; P = 0.004). DISCUSSION: ICCs and nNOS-positive cells reduced significantly in LES muscle of patients with achalasia. The number of ICCs differed among different achalasia subtypes and was related to patients' clinical prognosis.