BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is the most common cause of non-cardiac chest pain (NCCP). Currently available data reveal a weak relationship between NCCP and dysmotility. Moreover, it is unclear why some refluxes are perceived as heartburn and others as NCCP. We aimed to evaluate the role of the reflux pattern and the esophageal motility in patients with NCCP. METHODS: Forty-eight patients with NCCP (Group 1) and 50 only typical GERD symptoms (Group 2) were included and underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring. RESULTS: Impaired peristalsis was found in 60% of patients with NCCP and in 24% of patients with typical symptoms (P < 0.05). In patients belonging to Group 1, the majority of reflux episodes associated with chest pain were acid and mixed. The proportion of mixed refluxes was higher than that in Group 2. In Group 1, the reflux clearing time at 5, 9, and 15 cm, measured in reflux episodes associated to NCCP was longer than in reflux episodes associated to typical symptoms (mean ± 95% CI: 27.2 ± 5.6, 23.3 ± 4.4, and 14.6 ± 2.3 seconds vs 18.3 ± 3.5, 13.3 ± 2.2, and 11.1 ± 1.8 seconds; P < 0.01). CONCLUSIONS: The presence of gas in the refluxate seems to be associated with NCCP. The impaired motility observed in NCCP patients may play a relevant role in delaying reflux clearing, hence increasing the time of contact between refluxate and esophageal mucosa.
Chest Pain* ; Gastroesophageal Reflux ; Heartburn ; Humans ; Manometry ; Mucous Membrane ; Peristalsis ; Thorax*

Background/Aims: The role of esophageal high-resolution manometry (HRM) within Lyon consensus phenotypes, especially patients with inconclusive gastroesophageal reflux disease (GERD) evidence, has not been fully investigated. In this multicenter, observational study we aim to compare HRM parameters in patients with GERD stratified according to the Lyon consensus. Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH (MII-pH) studies performed off proton pump inhibitor therapy in patients with esophageal GERD symptoms were reviewed. Lyon consensus criteria identified pathological GERD, reflux hypersensitivity, functional heartburn, and inconclusive GERD. Patients, with inconclusive GERD were further subdivided into 2 groups based on total reflux numbers (≤ 80 or > 80 reflux episodes) during the MII-pH recording time. Results: A total of 264 patients formed the study cohort. Pathological GERD and inconclusive GERD patients were associated with higher numbers of reflux episodes, lower mean nocturnal baseline impedance (MNBI) values, and a higher proportion of patients with pathologic MNBI compared to functional heartburn (P < 0.05 for each comparison). On multivariate analysis, pathological GERD and inconclusive GERD patients, both with ≤ 80 or > 80 reflux episodes, were significantly associated with pathologic esophagogastric junction contractile integral values and with presence of hiatus hernia (type 2/3 esophagogastric junction). Patients with inconclusive GERD and > 80 reflux episodes were significantly associated with fragmented peristalsis and ineffective esophageal motility whilst inconclusive GERD with ≤ 80 reflux episodes were significantly associated with fragmented peristalsis. Conclusion Esophageal motor parameters on HRM are similar between pathologic and inconclusive GERD according to the Lyon consensus.

Background/Aims: The role of esophageal high-resolution manometry (HRM) within Lyon consensus phenotypes, especially patients with inconclusive gastroesophageal reflux disease (GERD) evidence, has not been fully investigated. In this multicenter, observational study we aim to compare HRM parameters in patients with GERD stratified according to the Lyon consensus. Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH (MII-pH) studies performed off proton pump inhibitor therapy in patients with esophageal GERD symptoms were reviewed. Lyon consensus criteria identified pathological GERD, reflux hypersensitivity, functional heartburn, and inconclusive GERD. Patients, with inconclusive GERD were further subdivided into 2 groups based on total reflux numbers (≤ 80 or > 80 reflux episodes) during the MII-pH recording time. Results: A total of 264 patients formed the study cohort. Pathological GERD and inconclusive GERD patients were associated with higher numbers of reflux episodes, lower mean nocturnal baseline impedance (MNBI) values, and a higher proportion of patients with pathologic MNBI compared to functional heartburn (P < 0.05 for each comparison). On multivariate analysis, pathological GERD and inconclusive GERD patients, both with ≤ 80 or > 80 reflux episodes, were significantly associated with pathologic esophagogastric junction contractile integral values and with presence of hiatus hernia (type 2/3 esophagogastric junction). Patients with inconclusive GERD and > 80 reflux episodes were significantly associated with fragmented peristalsis and ineffective esophageal motility whilst inconclusive GERD with ≤ 80 reflux episodes were significantly associated with fragmented peristalsis. Conclusion Esophageal motor parameters on HRM are similar between pathologic and inconclusive GERD according to the Lyon consensus.

Gastroesophageal reflux disease (GERD) is a complex disorder with heterogeneous symptoms and a multifaceted pathogenetic basis, which prevent a simple diagnostic algorithm or any categorical classification. Clinical history, questionnaires and response to proton pump inhibitor (PPI) therapy are insufficient tools to make a conclusive diagnosis of GERD and further investigations are frequently required. The Lyon Consensus goes beyond the previous classifications and defines endoscopic and functional parameters able to establish the presence of GERD. Evidences for reflux include high-grade erosive esophagitis, Barrett’s esophagus, and peptic strictures at endoscopy as well as esophageal acid exposure time > 6% on pH-metry or combined pH-impedance monitoring. Even if a normal endoscopy does not exclude GERD, its combination with distal acid exposure time < 4% on off-PPI pH-impedance monitoring provides sufficient evidence refuting this diagnosis. Reflux-symptom association on pH-monitoring provides supportive evidence for reflux-triggered symptoms and may predict a better treatment outcome, when present. Also recommendations to perform pH-impedance “on” or “off” PPI are well depicted. When endoscopy and pH-metry or combined pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (eg, microscopic esophagitis), high-resolution manometry (ie, ineffective esophagogastric barrier and esophageal body hypomotility), and novel impedance metrics, such as mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index, can contribute to better identify patients with GERD. Definition of individual patient phenotype, based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the esophagogastric junction, and clinical presentation, will lead to manage GERD patients with a tailored approach chosen among different types of therapy.

Background/Aims: Impaired esophageal motility and disrupted esophagogastric junction (EGJ) on high-resolution manometry (HRM) have been associated with increased reflux severity in gastroesophageal reflux disease (GERD) patients. However, there are limited data evaluating HRM parameters in proton pump inhibitors (PPI) non-responders. Methods: Clinical and endoscopic data, HRM and multichannel intraluminal impedance-pH studies performed of PPI therapy in patients with typical GERD symptoms were reviewed from 3 international centers. Frequency of GERD symptoms was assessed on and off PPI therapy in both non-responders (< 50% symptom improvement on PPI therapy) and responders. Rome IV definitions identified non-erosive reflux disease, reflux hypersensitivity, and functional heartburn. Univariate and multivariate analyses were performed to determine predictors of non-response. Results: Of 204 patients, 105 were PPI non-responders and 99 were responders. Non-responders showed higher EGJ contractile integral values, and a lower frequency of type II and III EGJ morphology (P ≤ 0.03 for each comparison). Esophageal body diagnoses on HRM (fragmented peristalsis, ineffective esophageal motility, or absent peristalsis) did not predict non-response. On multivariate analysis, non-pathological acid exposure time (OR, 2.5; 95% CI, 1.2-5.0; P < 0.001), normal mean nocturnal baseline impedance values (OR, 2.7-2.4; 95% CI, 1.0-6.1; P < 0.05), normal EGJ contractile integral values (OR, 3; 95% CI, 1.3-7.4; P = 0.012), and presence of type I EGJ morphology (OR, 1.9; 95% CI, 1.0-3.4;P = 0.044) were associated with an unfavorable response to PPIs. Conclusions Intact EGJ metrics on HRM complement normal reflux burden in predicting non-response to PPI therapy. HRM has value in the evaluation of PPI non-responders.

Background/Aims: Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. Methods: MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. Results: Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. Conclusion It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.

Background/Aims: Impaired intestinal motility seems to play a crucial role in symptomatic uncomplicated diverticular disease (SUDD), although the mechanism is not clear. The aim of the present study is to explore the contractility patterns of colonic smooth muscle strips (MS) and smooth muscle cells (SMCs) and to assess mucosal integrity in SUDD patients. Methods: MS or SMCs were isolated from specimens of human distal colon of 18 patients undergoing surgery for non-obstructive colonic cancer, among them 9 with SUDD. Spontaneous phasic contractions on strips and morpho-functional parameters on cells were evaluated in basal conditions and in response to acetylcholine (ACh). Mucosal integrity of SUDD colonic biopsies was evaluated by the Ussing Chamber system. Immunohistochemical staining for tight junction protein complex and for Toll-like receptor 4 (TLR4) was performed. Results: Colonic MS of SUDD group showed a significant reduced basal tone and ACh-elicited contraction, compared to the control group (9.5 g and 47.0% in the SUDD group; 14.16 g and 69.0% in the control group; P < 0.05). SMCs of SUDD group showed a maximal contractile response to ACh significantly reduced compared to control group (8.8% vs 16.5%, P < 0.05). SUDD patients displayed lower transepithelial electrical resistance and increased paracellular permeability compared to control group. Immunohistochemical expression of TLR4 was not different in both groups, while tight junction protein complex expression was lower in SUDD patients compared to control group patients. Conclusion It could be hypothesized that in SUDD, in absence of severe inflammation, an increased intestinal mucosal permeability is related to altered colonic motility probably responsible for symptoms genesis.