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Objective:To study reflux characteristics of patients with endoscopic negative heartburn and their manifestation under probe-based confocal laser endoscopy (pCLE) based on the Rome Ⅳ standard.Methods:Thirty-six endoscopic negative outpatients with typical heartburn at the Department of Gastroenterology of the Second Affiliated Hospital of Baotou Medical College from September 2020 to March 2021 were included, and underwent 24-hour multichannel intraluminal impedance-pH monitor and pCLE. According to Rome Ⅳ diagnostic process, patients were divided into non-erosive reflux disease (NERD) group ( n=16), reflux hypersensitivity (RH) group ( n=8) and functional heartburn (FH) group ( n=12). The Gerd-Q scale score, 24-hour pH monitoring results and microstructure changes under pCLE were compared among the three groups. Results:There was no significant difference in the total score, positive symptom score, negative symptom score or positive influence score of Gerd-Q scale among the three groups ( P>0.05). DeMeester score [28.45 (20.08, 34.53)] and acid reflux times (24.88±9.05) in the NERD group were significantly higher than those in the RH group [7.30 (3.90, 11.38), P<0.001; 13.63±5.76, P=0.003] and FH group [6.90 (4.80, 9.73), P<0.001; 7.42±8.32, P<0.001]. But there was no significant difference between the RH group and the FH group ( P>0.05). The diameter of intra-papillary capillary loop (IPCL) (18.68±2.12 μm) and dilation of intercellular space (3.95±0.97 μm) in the NERD group were significantly higher than those in the RH group (13.91±1.99 μm, P<0.001; 2.97±0.55 μm, P=0.006) and FH group (13.83±2.00 μm, P<0.001; 2.31±0.54 μm, P<0.001), but there was no significant difference between the RH group and the FH group ( P>0.05). The number of IPCL in the NERD group, RH group and FH group were 2.0 (1.00, 2.75), 2.0 (1.00, 2.75) and 1.5 (1.00, 2.00), respectively with no significant difference ( P=0.697). Conclusion:Gerd-Q scale is not suitable for differential diagnosis of patients with endoscopic negative heartburn. Compared with functional esophageal diseases (RH and FH), acid reflux and mucosal microstructure changes are of more important pathogenic significance in NERD.
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Objective:To investigate the role of ineffective esophageal motility (IEM) in non-erosive acid reflux related diseases, and the influence of the fourth edition Chicago classification (CC v4.0) on the diagnosis of IEM.Methods:From January 2018 to January 2020, 63 patients with acid reflux related symptoms who underwent gastroscopy and showed no abnormal changes in esophageal mucosa or structure, and underwent high resolution esophageal manometry (HRM) and 24-hour esophageal pH monitoring in the Department of Gastroenterology of Beijing Friendship Hospital were included in the case-control study. According to the HRM results, the third edition Chicago classification standard (CC v3.0) and CC v4.0 were used to divided patients into IEM group and normal dynamic group. The HRM results, 24-hour esophageal pH monitoring results and final diagnosis of the two groups under the two editions of Chicago classification standard were mainly compared and analyzed.Results:Among the 63 patients, there were 14 cases of non-erosive gastroesophageal reflux disease (NERD), 19 cases of reflux hypersensitivity (RH), and 30 cases of functional heartburn (FH). When using CC v3.0, there were 20 cases in the IEM group, including 9 cases of NERD, 5 cases of RH and 6 cases of FH, and 43 cases in the normal dynamic group, including 5 cases of NERD, 14 cases of RH and 24 cases of FH. When using CC v4.0, there were 16 cases in the IEM group, including 7 cases of NERD, 4 cases of RH and 5 cases of FH, and 47 cases in the normal dynamic group, including 7 cases of NERD, 15 cases of RH and 25 cases of FH. When using CC v3.0, compared with the normal dynamic group, the acid exposure time (AET) of the IEM group was significantly higher [3.45 (1.55, 6.40)% VS 1.20 (0.40, 2.30)%, Z=-2.940, P=0.003], the DeMeester score was also significantly higher [13.8 (5.8, 21.4) VS 5.3 (2.9, 10.0), Z=-2.851, P=0.004], the lower esophageal sphincter pressure (LESP) [10.15 (7.52, 13.65) mmHg (1 mmHg=0.133 kPa) VS 15.40 (11.20, 21.60) mmHg, Z=-3.241, P=0.001], 4-second integrated relaxation pressure (4sIRP) (3.79±0.57 mmHg VS 6.05±0.50 mmHg, t=2.727, P=0.008), and distal contraction integral (DCI) [334.65 (208.25, 438.92) mmHg·s·cm VS 1 258.70 (919.00, 1 750.10) mmHg·s·cm, Z=-6.305, P<0.001] were significantly lower than those of the normal dynamic group. When using CC v4.0, AET and Demeester scores in the IEM group were also significantly higher than those in the normal dynamic group (both P<0.05), and LESP, 4sIRP and DCI were also significantly lower than those in the normal dynamic group (all P<0.05). In addition, upper esophageal sphincter pressure was significantly lower than that in normal dynamic group [34.60 (21.50, 48.05) mmHg VS 49.67 (36.75, 61.10) mmHg, Z=-2.140, P=0.032]. Conclusion:IEM is associated with impaired anti-reflux barrier function and esophageal acid exposure in patients with non-erosive acid reflux related diseases. Compared with CC v3.0, CC v4.0 can reduce the heterogeneity of IEM patients to some extent.
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OBJECTIVE@#To analyze the differences in reflux patterns in 24-hour esophageal pH-impedance monitoring in patients with non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) and explore the possible mechanism of symptoms in patients with heartburn and negative endoscopic findings.@*METHODS@#Seventy-nine patients with heartburn as the main symptoms but negative endoscopic findings, including 35 with NERD, 16 with RH and 28 with FH, were enrolled in this study.All the patients underwent 24-h esophageal pH-impedance monitoring and esophagogastroscopy, and the results were compared among the 3 groups.@*RESULTS@#Acid reflux episode was significantly increased and weakly alkaline reflux episode was significantly decreased in NERD group in comparison with RH group and FH group (@*CONCLUSIONS@#Patients with NERD, RH and FH had different reflux patterns.Acid reflux is predominant in the NERD, while weakly alkaline reflux is significantly increased RH and FH.In patients with normal esophageal acid exposure but without symptoms or without recorded symptoms during esophageal pH-impedance monitoring, analysis of the total reflux episode, mixed reflux episode, proximal acid reflux episode and percentage can help in the differential diagnosis between RH and FH.
Subject(s)
Humans , Electric Impedance , Esophageal pH Monitoring , Gastroesophageal Reflux/diagnosis , Heartburn/etiology , Hydrogen-Ion ConcentrationABSTRACT
Objective To evaluate esophageal motility and anti-reflux barrier function in patients with different phenotypes of heartburn and negative endoscopic findings based on the Rome Ⅳ criteria.Methods From March 2011 to November 2018,136 patients with heartburn and negative endoscopic findings were retrospectively analyzed.The patients underwent high-resolution manometry (HRM),24-hour pH monitoring and proton pump inhibitor (PPI) test and according to the Rome Ⅳ criteria and new diagnostic procedures,they were divided into non-erosive reflux disease (NERD) group,reflux hypersensitivity (RH) group,functional heartburn (FH) group and unclassified group.During the same period,20 healthy volunteers were selected as healthy control group.The changes of esophageal motility and HRM were analyzed among different groups.Statistical analysis was performed using one-way analysis of variance,Kruskal-Wallis H test and chi-square test.Results According to Rome Ⅳ criteria,35 patients were enrolled into the NERD group,43 patients were enrolled into the RH group,48 patients were included in the FH group,and 10 patients were enrolled into unclassified group.There were no significant differences between the NERD group,the RH group,the FH group,the unclassified group and healthy control group in the length of the lower esophageal sphincter (LES),end lower esophageal sphincter resting pressure (LESP),mean LESP,4-second-integrated relaxation pressure (4 s-IRP),distal latency (DL),upper esophageal sphincter residual pressure (UES-RP),upper esophageal sphincter relaxation time to nadir,upper esophageal sphincter (UES) recovery time and esophagogastric junction contractile integral (EGJ-CI,all P ＞0.05).The distal contractile integral (DCI) of NERD group and unclassified group were both lower than that of healthy control group (919.7 mmHg · s · cm (411.7,1 417.9) mmHg· s · cm (1 mmHg =0.133 kPa),535.6 mmHg · s · cm (321.4,1 513.4) mmHg · s · cm vs.1 322.1 mmHg · s · cm (841.6,1 918.5) mmHg · s · cm),and the differences were statistically significant (Z =-2.62 and-2.20,P =0.01 and 0.03).The upper esophageal sphincter pressure (UESP) of the unclassified group was lower than that of the healthy control group (57.0 mmHg (31.3,77.8) mmHg vs.70.4 mmHg (49.4,97.8) mmHg),and the difference was statistically significant (Z =-2.64,P =0.02).There was significant difference in esophagogastric junction (EGJ) subtypes between the NERD group,the RH group,the FH group and the unclassified group (x2 =10.85,P =0.02);the proportion of type Ⅲ patients was highest in unclassified group,followed by NERD group,which were both higher than those of RH group and FH group.There was no significant difference in the proportion of esophageal motility subtypes between NERD group,RH group,FH group and unclassified group (P ＞ 0.05).Conclusions Patients with different phenotypes of heartburn and negative endoscopy finding should be classified by efficient diagnostic procedure according to the Rome Ⅳ criteria combined with HRM,24-hour pH monitoring and PPI test.The unclassified patients need further evaluation,especially for those with effective PPI test and negative pH monitoring.However,the evaluation of anti-reflux barrier function by the HRM parameters in patients with heartburn and negative endoscopic findings has certain limitations.
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Objective@#To evaluate esophageal motility and anti-reflux barrier function in patients with different phenotypes of heartburn and negative endoscopic findings based on the Rome Ⅳ criteria.@*Methods@#From March 2011 to November 2018, 136 patients with heartburn and negative endoscopic findings were retrospectively analyzed. The patients underwent high-resolution manometry (HRM), 24-hour pH monitoring and proton pump inhibitor (PPI) test and according to the Rome Ⅳ criteria and new diagnostic procedures, they were divided into non-erosive reflux disease (NERD) group, reflux hypersensitivity (RH) group, functional heartburn (FH) group and unclassified group. During the same period, 20 healthy volunteers were selected as healthy control group. The changes of esophageal motility and HRM were analyzed among different groups. Statistical analysis was performed using one-way analysis of variance, Kruskal-Wallis H test and chi-square test.@*Results@#According to Rome Ⅳ criteria, 35 patients were enrolled into the NERD group, 43 patients were enrolled into the RH group, 48 patients were included in the FH group, and 10 patients were enrolled into unclassified group. There were no significant differences between the NERD group, the RH group, the FH group, the unclassified group and healthy control group in the length of the lower esophageal sphincter (LES), end lower esophageal sphincter resting pressure (LESP), mean LESP, 4-second-integrated relaxation pressure (4 s-IRP), distal latency (DL) , upper esophageal sphincter residual pressure (UES-RP), upper esophageal sphincter relaxation time to nadir, upper esophageal sphincter (UES) recovery time and esophagogastric junction contractile integral (EGJ-CI, all P>0.05). The distal contractile integral (DCI) of NERD group and unclassified group were both lower than that of healthy control group (919.7 mmHg·s·cm (411.7, 1 417.9) mmHg·s·cm (1 mmHg=0.133 kPa), 535.6 mmHg·s·cm (321.4, 1 513.4) mmHg·s·cm vs. 1 322.1 mmHg·s·cm (841.6, 1 918.5) mmHg·s·cm), and the differences were statistically significant (Z=-2.62 and -2.20, P=0.01 and 0.03). The upper esophageal sphincter pressure (UESP) of the unclassified group was lower than that of the healthy control group(57.0 mmHg (31.3, 77.8) mmHg vs. 70.4 mmHg (49.4, 97.8) mmHg), and the difference was statistically significant (Z=-2.64, P=0.02). There was significant difference in esophagogastric junction (EGJ) subtypes between the NERD group, the RH group, the FH group and the unclassified group (χ2=10.85, P=0.02); the proportion of type Ⅲ patients was highest in unclassified group, followed by NERD group, which were both higher than those of RH group and FH group. There was no significant difference in the proportion of esophageal motility subtypes between NERD group, RH group, FH group and unclassified group (P>0.05).@*Conclusions@#Patients with different phenotypes of heartburn and negative endoscopy finding should be classified by efficient diagnostic procedure according to the Rome Ⅳ criteria combined with HRM, 24-hour pH monitoring and PPI test. The unclassified patients need further evaluation, especially for those with effective PPI test and negative pH monitoring. However, the evaluation of anti-reflux barrier function by the HRM parameters in patients with heartburn and negative endoscopic findings has certain limitations.
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The Rome IV criteria, published in 2016, encompass upper gastrointestinal lesions of functional esophageal disorders and functional gastroduodenal disorders. Functional esophageal disorders include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. Patients with functional esophageal disorders typically have esophageal symptoms that are not associated with structural, inflammatory, or major esophageal motor disorders. Although the mechanisms of symptom generation in functional esophageal disorders are unclear, visceral hypersensitivity and hypervigilance may play a role. Therefore, treatment options include drugs and modalities that affect peripheral triggering and central perception. Further well-designed studies are needed to identify the mechanisms of symptom generation in, and to develop appropriate therapies for, functional esophageal disorders.
Subject(s)
Humans , Anxiety , Chest Pain , Deglutition Disorders , Heartburn , Hypersensitivity , Motor DisordersABSTRACT
Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.
Subject(s)
Female , Humans , Middle Aged , Biopsy , Chest Pain , Comorbidity , Diagnosis , Endoscopy , Esophagus , Gastrointestinal Diseases , Heartburn , Hydrogen-Ion Concentration , Hypersensitivity , Manometry , Neurotransmitter Agents , Proton Pumps , Selective Serotonin Reuptake InhibitorsABSTRACT
About one-third of patients with suspected gastro-oesophageal reflux disease (GERD) do not respond symptomatically to proton pump inhibitors (PPIs). Many of these patients do not suffer from GERD, but may have underlying functional heartburn or atypical chest pain. Other causes of failure to respond to PPIs include inadequate acid suppression, non-acid reflux, oesophageal hypersensitivity, oesophageal dysmotility and psychological comorbidities. Functional oesophageal tests can exclude cardiac and structural causes, as well as help to confi rm or exclude GERD. The use of PPIs should only be continued in the presence of acid reflux or oesophageal hypersensitivity for acid reflux-related events that is proven on functional oesophageal tests.