Role of Mixed Reflux and Hypomotility with Delayed Reflux Clearance in Patients with Non-cardiac Chest Pain

( Mentore Ribolsi ),( Paola Balestrieri ),( Dario Biasutto ),( Sara Emerenziani ),( Michele Cicala ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.4

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 highresolution 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.

High-resolution Manometry Findings During Solid Swallows Correlate With Delayed Reflux Clearance and Acid Exposure Time in Non-erosive Reflux Disease Patients

Mentore Ribolsi,Dario Biasutto,Antonio Giordano,Paola Balestrieri,Michele Cicala 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.1

Background/Aims The role of esophageal motility in determining gastroesophageal reflux disease (GERD) severity has not been completely evaluated. A few studies have investigated high-resolution manometry (HRM) patterns during solid swallows. The present study evaluates the HRM patterns of non-erosive reflux disease (NERD) patients during both liquid and solid swallows and their correlation with the severity of GERD. Methods In 23 NERD patients and 15 healthy volunteers (HVs) HRM was performed during a standard solid meal in a seated position, followed by 24-hour impedance-pH monitoring. Results Of the 31 patients, 10 showed a pathological acid exposure time (AET; NERD patients), 13 a normal pH profile with positive symptom association probability (SAP; reflux hypersensitivity patients), and 8 normal AET and SAP (functional heartburn patients). Mean distal contractile integral and distal latency values, in all patient groups and HVs, were significantly higher during solid swallows. In the group of 10 NERD patients, the number of large breaks of the esophageal peristalsis was 16 out of 100 liquid swallows (16%) and 31 out of 171 solid swallows (18%). Fourteen out of 100 liquid swallows (14%) and 25 out of 171 solid swallows (15%) resulted ineffective. Mean reflux clearing time at multichannel intraluminal impedance-pH was 17.6 ± 3.7 seconds. NERD patients presented, during solid swallows, a significantly higher proportion of large peristaltic breaks and of ineffective swallows than reflux hypersensitivity and functional heartburn patients. Conclusion HRM during solid swallows reveals motor abnormalities, undetected during liquid swallows, which might be involved in delaying reflux and acid clearance in patients with GERD.

Impaired Colonic Contractility and Intestinal Permeability in Symptomatic Uncomplicated Diverticular Disease

( Annamaria Altomare ),( Manuele Gori ),( Silvia Cocca ),( Simone Carotti ),( Maria Francesconi ),( Mentore Ribolsi ),( Sara Emerenziani ),( Giuseppe Perrone ),( Sergio Morini ),( Michele Cicala ),( M 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.2

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. (J Neurogastroenterol Motil 2021;27:292-301)

High-resolution Manometry Determinants of Refractoriness of Reflux Symptoms to Proton Pump Inhibitor Therapy

( Mentore Ribolsi ),( Edoardo Savarino ),( Benjamin Rogers ),( Arvind Rengarajan ),( Marco Della Coletta ),( Matteo Ghisa ),( Michele Cicala ),( C Prakash Gyawali ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.4

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. (J Neurogastroenterol Motil 2020;26:447-454)

Patients With Definite and Inconclusive Evidence of Reflux According to Lyon Consensus Display Similar Motility and Esophagogastric Junction Characteristics

( Mentore Ribolsi ),( Edoardo Savarino ),( Benjamin Rogers ),( Arvind Rengarajan ),( Marco Della Coletta ),( Matteo Ghisa ),( Michele Cicala ),( C Prakash Gyawali ) 대한소화기기능성질환·운동학회 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.4

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. (J Neurogastroenterol Motil 2021;27:565-573)