BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophag...BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis(EE)and non-erosive forms of GERD(NERD)and its association with data of esophageal multichannel intraluminal impedancepH(MII-pH)measurements.METHODS This was a single-center prospective study.Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy.Expression of interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factorα(TNFA),toll-like receptor 4(TLR4),GATA binding protein 3(GATA3),differentiation cluster 68(CD68)andβ-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays.MII-pH measurements were performed on all the participants.Diagnosis of GERD was confirmed by the results of the MII-pH data.Based on the endoscopy,patients were allocated to the groups of EE and NERD.The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results.We used nonparametric statistics to compare the differences between the groups.Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTS Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis.Higher expression of IL-18(5.89±0.4 vs 5.28±1.1,P=0.04)and GATA3(2.92±0.86 vs 2.23±0.96,P=0.03)was found in the EE group compared to NERD.Expression of IL-1β,IL-18,TNFA,and TLR4 was lower(P<0.05)in the control group compared to EE and NERD.Esophageal acid exposure correlated with the expression of IL-1β(Spearman’s rank r=0.29),IL-18(r=0.31),TNFA(r=0.35),GATA3(r=0.34),TLR4(r=0.29),and CD68(r=0.37).Mean esophagealрНcorrelated inversely with the expression of IL-18,TNFA,GATA3,TLR4,and CD68.No association of gene expression with the number of gastroesophageal refluxes was found.CONCLUSION In patients with EE,local expression of IL-18 and GATA3 was higher compared to subjects with NERD.Esophageal acid exposure correlated directly with expression of IL-1β,IL-18,TNFA,TLR4,CD68,andβ-2 microglobulin genes.Inverse correlation was revealed between expression of IL-18,TNFA,GATA3,TLR4,and CD68 and mean esophageal pH.展开更多
Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often a...Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor (PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total (360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior (Toupet) fundoplication, and the anterior (Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.展开更多
AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg t...AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.展开更多
BACKGROUND Diagnosing laryngopharyngeal reflux(LPR)is challenging due to overlapping symptoms.While proton pump inhibitors(PPIs)are commonly prescribed,reliable predictors of their responsiveness are unclear.Reflux mo...BACKGROUND Diagnosing laryngopharyngeal reflux(LPR)is challenging due to overlapping symptoms.While proton pump inhibitors(PPIs)are commonly prescribed,reliable predictors of their responsiveness are unclear.Reflux monitoring techno-server reliability.We hypothesized that PAR episodes alone might also predict PPI responsiveness.AIM To investigate whether PAR episodes alone predict a positive response to PPI therapy.METHODS Patients suspected of having LPR were prospectively recruited from otolaryngologic clinics in three Taiwan residents tertiary centers.They underwent a 24-hour esophagopharyngeal pH test using either 3-pH-sensor or hypopha-ryngeal MII-pH catheters while off medication,followed by a 12-week esomeprazole course(40 mg twice daily).Participants were categorized into four groups based on pH results:PAR alone,EAR alone,both pH(+),and both pH(-).The primary outcome was a≥50%reduction in primary laryngeal symptoms,with observers blinded to group assignments.RESULTS A total of 522 patients(mean age 52.3±12.8 years,54%male)were recruited.Of these,190(mean age 51.5±12.4 years,61%male)completed the treatment,and 89(47%)responded to PPI therapy.Response rates were highest in the PAR alone group(73%,n=11),followed by EAR alone(59%,n=68),both pH(+)(56%,n=18),and both pH(-)(33%,n=93).Multivariate analysis adjusting for age,sex,body mass index,and endoscopic esophagitis showed that participants with PAR alone,EAR alone,and both pH(+)were 7.4-fold(P=0.008),4.2-fold(P=0.0002),and 3.4-fold(P=0.03)more likely to respond to PPI therapy,respectively,compared to the both pH(-)group.Secondary analyses using the definition of≥1 PAR episode were less robust.CONCLUSION In the absence of proven hypopharyngeal predictors,this post-hoc analysis found that baseline≥2 PAR episodes alone are linked to PPI responsiveness,suggesting the importance of hypopharyngeal reflux monitoring.展开更多
Heartburn is among the most common gastrointestinal symptoms presenting to both generalist physicians and gastroenterologists.In the era of high utilization of proton pump inhibitors,a substantial proportion of patien...Heartburn is among the most common gastrointestinal symptoms presenting to both generalist physicians and gastroenterologists.In the era of high utilization of proton pump inhibitors,a substantial proportion of patients presenting to the gastroenterologist with chronic symptoms of heartburn do not have a reflux-mediated disease.Subjects without objective evidence of reflux as a cause of their symptoms have functional heartburn(FH).FH has no evidence of abnormal esophageal acid exposure on ambulatory reflux monitoring,major esophageal motor disorders on high resolution manometry,or esophageal mucosal pathology,such as eosinophilic esophagitis on endoscopy with esophageal biopsies.The pathophysiology of FH is unknown but it is often associated with visceral hypersensitivity,and psychiatric disease.Importantly,anti-reflux surgery or other invasive anti-reflux modalities should be avoided.Although there are limited supporting data,modulation of pain perception,traditional Chinese medicine and psychological intervention may be potential therapeutic options in this population.展开更多
基金Supported by Ministry of Science and Higher Education,No.FGMF-2022-0005 and No.0410-2020-0007。
文摘BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis(EE)and non-erosive forms of GERD(NERD)and its association with data of esophageal multichannel intraluminal impedancepH(MII-pH)measurements.METHODS This was a single-center prospective study.Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy.Expression of interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factorα(TNFA),toll-like receptor 4(TLR4),GATA binding protein 3(GATA3),differentiation cluster 68(CD68)andβ-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays.MII-pH measurements were performed on all the participants.Diagnosis of GERD was confirmed by the results of the MII-pH data.Based on the endoscopy,patients were allocated to the groups of EE and NERD.The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results.We used nonparametric statistics to compare the differences between the groups.Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTS Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis.Higher expression of IL-18(5.89±0.4 vs 5.28±1.1,P=0.04)and GATA3(2.92±0.86 vs 2.23±0.96,P=0.03)was found in the EE group compared to NERD.Expression of IL-1β,IL-18,TNFA,and TLR4 was lower(P<0.05)in the control group compared to EE and NERD.Esophageal acid exposure correlated with the expression of IL-1β(Spearman’s rank r=0.29),IL-18(r=0.31),TNFA(r=0.35),GATA3(r=0.34),TLR4(r=0.29),and CD68(r=0.37).Mean esophagealрНcorrelated inversely with the expression of IL-18,TNFA,GATA3,TLR4,and CD68.No association of gene expression with the number of gastroesophageal refluxes was found.CONCLUSION In patients with EE,local expression of IL-18 and GATA3 was higher compared to subjects with NERD.Esophageal acid exposure correlated directly with expression of IL-1β,IL-18,TNFA,TLR4,CD68,andβ-2 microglobulin genes.Inverse correlation was revealed between expression of IL-18,TNFA,GATA3,TLR4,and CD68 and mean esophageal pH.
文摘Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor (PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total (360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior (Toupet) fundoplication, and the anterior (Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.
文摘AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.
文摘BACKGROUND Diagnosing laryngopharyngeal reflux(LPR)is challenging due to overlapping symptoms.While proton pump inhibitors(PPIs)are commonly prescribed,reliable predictors of their responsiveness are unclear.Reflux monitoring techno-server reliability.We hypothesized that PAR episodes alone might also predict PPI responsiveness.AIM To investigate whether PAR episodes alone predict a positive response to PPI therapy.METHODS Patients suspected of having LPR were prospectively recruited from otolaryngologic clinics in three Taiwan residents tertiary centers.They underwent a 24-hour esophagopharyngeal pH test using either 3-pH-sensor or hypopha-ryngeal MII-pH catheters while off medication,followed by a 12-week esomeprazole course(40 mg twice daily).Participants were categorized into four groups based on pH results:PAR alone,EAR alone,both pH(+),and both pH(-).The primary outcome was a≥50%reduction in primary laryngeal symptoms,with observers blinded to group assignments.RESULTS A total of 522 patients(mean age 52.3±12.8 years,54%male)were recruited.Of these,190(mean age 51.5±12.4 years,61%male)completed the treatment,and 89(47%)responded to PPI therapy.Response rates were highest in the PAR alone group(73%,n=11),followed by EAR alone(59%,n=68),both pH(+)(56%,n=18),and both pH(-)(33%,n=93).Multivariate analysis adjusting for age,sex,body mass index,and endoscopic esophagitis showed that participants with PAR alone,EAR alone,and both pH(+)were 7.4-fold(P=0.008),4.2-fold(P=0.0002),and 3.4-fold(P=0.03)more likely to respond to PPI therapy,respectively,compared to the both pH(-)group.Secondary analyses using the definition of≥1 PAR episode were less robust.CONCLUSION In the absence of proven hypopharyngeal predictors,this post-hoc analysis found that baseline≥2 PAR episodes alone are linked to PPI responsiveness,suggesting the importance of hypopharyngeal reflux monitoring.
文摘Heartburn is among the most common gastrointestinal symptoms presenting to both generalist physicians and gastroenterologists.In the era of high utilization of proton pump inhibitors,a substantial proportion of patients presenting to the gastroenterologist with chronic symptoms of heartburn do not have a reflux-mediated disease.Subjects without objective evidence of reflux as a cause of their symptoms have functional heartburn(FH).FH has no evidence of abnormal esophageal acid exposure on ambulatory reflux monitoring,major esophageal motor disorders on high resolution manometry,or esophageal mucosal pathology,such as eosinophilic esophagitis on endoscopy with esophageal biopsies.The pathophysiology of FH is unknown but it is often associated with visceral hypersensitivity,and psychiatric disease.Importantly,anti-reflux surgery or other invasive anti-reflux modalities should be avoided.Although there are limited supporting data,modulation of pain perception,traditional Chinese medicine and psychological intervention may be potential therapeutic options in this population.
