Deglutitive Inhibition, Latency Between Swallow and Esophageal Contractions and Primary Esophageal Motor Disorders

( Daniel Sifrim ),( Jafar Jafari ) 대한소화기기능성질환·운동학회 (구 대한소화관운동학회) 2012 Journal of Neurogastroenterology and Motility (JNM Vol.18 No.1

Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm. (J Neurogastroenterol Motil 2012;18:6-12)

Esophageal Baseline Impedance Reflects Mucosal Integrity and Predicts Symptomatic Outcome With Proton Pump Inhibitor Treatment

( Chenxi Xie ),( Daniel Sifrim ),( Yuwen Li ),( Minhu Chen ),( Yinglian Xiao ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.1

Background/Aims Esophageal baseline impedance, which is decreased in gastroesophageal reflux disease (GERD) patients, is related to the severity of acid reflux and the integrity of the esophageal mucosa. The study aims to compare the baseline impedance and the dilated intercellular spaces (DIS) within patients with typical reflux symptoms and to evaluate the correlation of baseline impedance with DIS, esophageal acid exposure, as well as the efficacy of proton pump inhibitor (PPI) treatment. Methods Ninety-two patients and 10 healthy controls were included in the study. Erosive esophagitis (EE) was defined by esophageal mucosal erosion under upper endoscopy. Patients without mucosa erosion were divided into groups with pathologic acid reflux (non-erosive reflux disease [NERD]) or with hypersensitive esophagus. The biopsies of esophageal mucosa were taken 2-4 cm above the gastroesophageal junction Z-line during upper endoscopy for DIS measurement. All the patients received esomeprazole 20 mg twice-daily treatment for 8 weeks. The efficacy of esomeprazole was evaluated among all patients. Results The intercellular spaces were dilated in both EE and NERD patients (P < 0.05). The value 0.73 mm could be used as the cut-off DIS value to distinguish patients from controls (area under the curve [AUC] = 0.849, P < 0.01). One thousand seven hundred sixty-four ohms could be used as the cut-off impedance values to distinguish patients from controls (AUC = 0.794, P < 0.01). The baseline impedance was decreased in both EE patients and NERD patients, and negatively correlated to the acid exposure time (r = -0.527, P < 0.05). There was a weak correlation between DIS and baseline impedance (r = -0.230, P < 0.05). “Baseline impedance > 1764 Ω” was an independent predictor for PPI failure (OR, 11.9; 95% CI, 2.4-58.9; P < 0.01). Conclusions The DIS and decreased baseline impedance was observed in patients with mucosa erosion or pathological acid reflux. The baseline impedance reflected the mucosal integrity, it was more sensitive to esophageal acid exposure. Patients with high impedance might not benefit from the PPI treatment. (J Neurogastroenterol Motil 2018;24:43-50)

Esophageal Reflux Hypersensitivity: A Comprehensive Review

Sawada Akinari,Sifrim Daniel,Fujiwara Yasuhiro 거트앤리버 소화기연관학회협의회 2023 Gut and Liver Vol.17 No.6

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts’ consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

The Role of Weakly Acidic Reflux in Proton Pump Inhibitor Failure, Has Dust Settled?

( Emmanouela Tsoukali ),( Daniel Sifrim ) 대한소화관운동학회 2010 Journal of Neurogastroenterology and Motility (JNM Vol.16 No.3

Patients that do not respond satisfactorily to standard proton pump inhibitor (PPI) treatment have become the most common presentation of gastro-esophageal reflux disease (GERD) in third referral gastrointestinal practices. The causes of refractory GERD include lack of compliance with treatment, residual acid reflux and weakly acidic reflux, esophageal hypersensitivity and persistent symptoms not associated with reflux. A role for weakly acidic reflux in symptom generation has been proposed since the availability of impedance-pH monitoring. The possible mechanisms by which persistent weakly acidic reflux might contri-bute to persistent symptoms in patients under PPI treatment may include esophageal distension by increased reflux volume, persistent impaired mucosal integrity (ie, dilation of intercellular spaces) and/or esophageal hypersensitivity to weakly acidic re-flux events. To establish a definite role of weakly acidic reflux in refractory GERD, outcome studies targeting this type of reflux are still lacking. Treatment strategies to reduce the number or effect of weakly acidic reflux could involve drugs that decrease transient lower esophageal sphincter relaxations (ie, baclofen or similar), improve oesophageal mucosa resistance or visceral pain modulators. Finally, anti-reflux surgery can be considered, only if a clear symptom-weakly acidic reflux association was demonstrated.

Relationship Between Salivary Pepsin Concentration and Esophageal Mucosal Integrity in Patients With Gastroesophageal Reflux Disease

( Yu-wen Li ),( Daniel Sifrim ),( Chenxi Xie ),( Minhu Chen ),( Ying-lian Xiao ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.4

Background/Aims Increased salivary pepsin could indicate an increase in gastro-esophageal reflux, however, previous studies failed to demonstrate a correlation between salivary pepsin concentrations and 24-hour esophageal acid exposure. This study aims to detect the salivary pepsin and to evaluate the relationship between salivary pepsin concentrations and intercellular spaces (IS) in different gastroesophageal reflux disease phenotypes in patients. Methods A total of 45 patients and 11 healthy volunteers were included in this study. All subjects underwent upper gastrointestinal endoscopy, 24-hour ambulatory multichannel impedance-pH (MII-pH) monitoring, and salivary sampling at 3-time points during the 24-hour MII-pH monitoring. IS were measured by transmission electron microscopy, and salivary pepsin concentrations were determined by enzyme-linked immunosorbent assay. Results The IS measurements were greater in the esophagitis (EE), non-erosive reflux disease (NERD), and hypersensitive esophagus (HO) groups than in the functional heartburn (FH) and healthy volunteer groups, and significant differences were indicated. Patients with NERD and HO had higher average pepsin concentrations compared with FH patients. A weak correlation was determined between IS and salivary pepsin among patients with NERD (r = 0.669, P = 0.035). Conclusions We confirmed the presence of a higher level of salivary pepsin in patients with NERD than in patients with FH. Salivary pepsin concentrations correlated with severity of mucosal integrity impairment in the NERD group. We suggest that in patients with NERD, low levels of salivary pepsin can help identify patients with FH, in addition the higher the pepsin concentration, the more likely the severity of dilated IS. (J Neurogastroenterol Motil 2017;23:517-525)

Editorial : Use of Solid Boluses in High-resolution Manometry

( Yu Tien Wang ),( Daniel Sifrim ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.4

Review : High-resolution Manometry: Esophageal Disorders Not Addressed by the “Chicago Classification”

( Yu Tien Wang ),( Etsuro Yazaki ),( Daniel Sifrim ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2012 Journal of Neurogastroenterology and Motility (JNM Vol.18 No.4

The development of the high-resolution esophageal manometry (HRM) and the Chicago classification have improved the diagnosis and management of esophageal motility disorders. However, some conditions have yet to be addressed by this classification. This review describes findings in HRM which are not included in the current Chicago classification based on the experience in our center. This includes the analysis of the upper esophageal sphincter, proximal esophagus, longitudinal muscle contraction, disorders related to gastroesophageal reflux disease and respiratory symptoms. The utility of provocative tests and the use of HRM in the evaluation of rumination syndrome and post-surgical patients will also be discussed. We believe that characterization of the manometric findings in these areas will eventually lead to incorporation of new criteria into the existing classification. (J Neurogastroenterol Motil 2012,18:365-372)

Supragastric Belching: Prevalence and Association With Gastroesophageal Reflux Disease and Esophageal Hypomotility

( Nikolaos Koukias ),( Philip Woodland ),( Etsuro Yazaki ),( Daniel Sifrim ) 대한소화기기능성질환·운동학회 2015 Journal of Neurogastroenterology and Motility (JNM Vol.21 No.3

Background/Aims: Supragastric belching (SGB) is a phenomenon during which air is sucked into the esophagus and then rapidly expelled through the mouth. Patients often complain of severely impaired quality of life. Our objective was to establish the prevalence of excessive SGB within a high-volume gastrointestinal physiology unit, and evaluate its association with symptoms, esophageal motility and gastresophageal reflux disease. Methods: We established normal values for SGB by analyzing 24-hour pH-impedance in 40 healthy asymptomatic volunteers. We searched 2950 consecutive patient reports from our upper GI Physiology Unit (from 2010-2013) for SGB. Symptoms were recorded by a standardized questionnaire evaluating for reflux, dysphagia, and dyspepsia symptoms. We reviewed the predom - inant symptoms, 24-hour pH-impedance and high-resolution esophageal manometry results. Results: Excessive SGB was defined as > 13 per 24 hours. We identified 100 patients with excessive SGB. Ninety-five percent of these patients suffered from typical reflux symptoms, 86% reported excessive belching, and 65% reported dysphagia. Forty-one percent of patients with excessive SGB had pathological acid reflux. Compared to the patients with normal acid exposure these patients trended towards a higher number of SGB episodes. Forty-four percent of patients had esophageal hypomotility. Patients with hypomotility had a significantly higher frequency of SGB compared to those with normal motility (118.3 ± 106.1 vs 80.6 ± 75.7, P = 0.020). Conclusions: Increased belching is rarely a symptom in isolation. Pathological acid exposure and hypomotility are associated with more SGB frequency. Whether SGB is a disordered response to other esophageal symptoms or their cause is unclear. (J Neurogastroenterol Motil 2015;21:398-403)

Measurement of Esophageal Nocturnal Baseline Impedance: A Simplified Method

( Yoshimasa Hoshikawa ),( Akinari Sawada ),( Shirley Sonmez ),( Kornilia Nikaki ),( Philip Woodland ),( Etsuro Yazaki ),( Daniel Sifrim ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2020 Journal of Neurogastroenterology and Motility (JNM Vol.26 No.2

Background/Aims Mean nocturnal baseline impedance (MNBI) during multichannel intraluminal impedance pH-monitoring (MII-pH) reflects the status of esophageal mucosal integrity. MNBI is suggested as an adjunctive method to distinguish patients with true gastroesophageal reflux disease (GERD) from functional heartburn (FH) and might predict outcomes for anti-reflux treatment. However, current methodology for calculation of MNBI is time-consuming and subject to operator-dependent selection bias. We aim to simplify and provide a more objective method to calculate MNBI. Methods We retrospectively analyzed 100 MII-pH tracings from 20 patients with erosive reflux disease, 20 with non-erosive reflux disease (NERD), 20 with reflux hypersensitivity, 20 with functional heartburn (FH), and 20 healthy asymptomatic volunteers. We compared the current “conventional” MNBI analysis with our “simple” MNBI analysis measured by selecting the whole supine period using the impedance average calculation function in the MII-pH software. Results Absolute values were very similar and there was a strong correlation between conventional and simple MNBI values in the most distal channel in all groups (r ≥ 0.8, P < 0.001) including patients with increased supine acid reflux. Distal esophageal simple MNBI negatively correlated with acid exposure time (r = -0.695, P < 0.001). Patients with erosive reflux disease and NERD had lower simple MNBI values in the most distal channel compared to other groups (P < 0.001). With a cutoff value of 1785 ohms, simple MNBI can discriminate patients with GERD from those with reflux hypersensitivity and FH (sensitivity 80.0% and specificity 89.7%). Conclusion Simple MNBI analysis provides very similar values and has an excellent correlation with conventional MNBI analysis. (J Neurogastroenterol Motil 2020;26:241-247)

Nocturnal Gastroesophageal Reflux Revisited by Impedance-pH Monitoring

( Fernando Fornari ),( Kathleen Blondeau ),( Veerle Mertens ),( Jan Tack ),( Daniel Sifrim ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2011 Journal of Neurogastroenterology and Motility (JNM Vol.17 No.2

Background/Aims Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux. Methods Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described. Results Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity. Conclusions Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux. (J Neurogastroenterol Motil 2011;17:148-157)