Altered Esophageal Mechanosensitivity of Secondary Peristalsis as a Pathophysiological Marker in Patients with Globus Sensation

ml thin barium. HRIM of five 5-ml saline swallows in the upright position was analyzed with a customized MATLAB program to calculate the EII ratio, and IBH was quantified following ingestion of 200-ml saline. Correlations of Eckardt score using Spearman's rho were assessed for each measure. Receiver-operating characteristic curves for good symptomatic outcome (Eckardt score <4) were generated for each potential predictor. Outcome groups were compared using Mann-Whitney U test. Results: Follow-up occurred at a median (range) 12 (3-183) months following treatment. 46 patients had good symptomatic outcomes. Correlation coefficient between Eckardt scores and potential predictors were .50 (p=.000) for EII ratio, .30 (p=.014) for IBH, .36 (p=.003) for TBE width, .39 (p=.001) for TBE height, and .47 (p=.000) for TBE area. Comparison of symptomatic outcome was significant for EII ratio (p=.000), IBH (p=.001), TBE height (p=.000), and TBE area (p=.000) [Figure1]. Receiver-operating characteristic curves for good symptomatic outcome were generated [Figure 2]. The area-under-the-curves were .80 (95% CI [.68-.93]) for EII ratio, .75 (95% CI [.62-.88]) for IBH, and .78 (95% CI [.65-.90]) for TBE area. Optimal cut-points were determined as 0.40 (EII ratio), 7.5 mm (IBH), 5.10 mm (TBE height), and 3.85 mm2 (TBE area), that provided sensitivities/specificities of 77%/20% (EII ratio), 68%/27% (IBH), 55%/ 22% (TBE height), and 86%/33% (TBE area) to predict symptomatic outcome. Conclusions: Novel HRIM metrics, EII ratio and IBH, correlate well with symptoms. Moreover, TBE area has a somewhat stronger correlation than the more commonly used TBE height. These measures could improve clinical evaluation of treatment response.

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Baseline characteristics associated with long-term follow-up symptom score

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Compared via Chi-squared tests. Values indicate number (%) of patients with characteristic present, unless otherwise stated. 2Compared via Mann-Whitney U tests. Values indicate median (range).

Sa1651 LOWER ESOPHAGEAL SPHINCTER (LES) RECEPTIVE RELAXATION IS INDISPENSABLE FOR SUCCESSFUL LES RELAXATION IN WET SWALLOWING Kazumasa Muta, Eikichi Ihara, Keita Fukaura, Xiaopeng Bai, Shouhei Hamada, Toshiaki Ochiai, Tsutomu Iwasa, Akira Aso, Kazuhiko Nakamura Figure 1. Comparison of high-resolution impedance manometry and timed barium esophagram metrics across good versus poor symptomatic outcomes. Patients with more severe symptoms had higher EII ratio, higher IBH, higher TBE height, and larger TBE area. EII ratio, esophageal impedance integral; IBH, impedance bolus height; TBE, timed barium esophagram; ES, Eckardt's score.

Background and Aim: Based on the Chicago classification ver3.0, disorders of esophagogastric junction (EGJ) outflow obstruction are characterized by impaired lower esophageal sphincter (LES) relaxation. Two mechanisms cause LES relaxation: pharyngeal water stimulation (PWS)-induced LES relaxation (Mittal, RK et. al. Gastroenterology) and swallow-induced LES relaxation. PWS-induced LES relaxation appears to correspond to gastric receptive relaxation, and thus could be called LES receptive relaxation. The relative contribution of LES receptive relaxation and swallow-induced LES relaxation to normal esophageal motility function is unknown. This study aimed to evaluate how receptive LES relaxation contributes to normal esophageal motility function. Method: Fourteen participants with normal highresolution manometry (HRM) results (mean age, 50.0 ± 3.0 years) were enrolled. The participants were asked to perform a dry swallow 5 times and then a wet swallow when drinking 5 ml of water 5 times. Basal LES pressure (BLESP) and integrated relaxation pressure (IRP) were measured. The extent of LES receptive relaxation (mmHg) was calculated by the following formula: A−B, where A is the mean LES pressure for 5 s just before PWS stimulation and B is the mean LES pressure during PWS for 5 s just before initiating each liquid swallow. The extent of swallow-induced LES relaxation (mmHg) was calculated by the following formula: B−C, where B is as mentioned above and C is the IRP at each swallow. Result: There was no significant difference in BLESP between before (30.9 ± 3 mmHg) and after (29.6 ± 2.4 mmHg) dry swallowing. The extent of LES relaxation in dry swallowing was smaller than that found in wet swallowing. The mean IRP of dry swallowing (19.25 ± 2.1 mmHg) was significantly higher than that of wet swallowing (10 ± 0.7 mmHg). HRM findings in dry swallowing were similar to those observed in patients with EGJ outflow obstruction characterized by impaired LES receptive relaxation. As a result, LES receptive relaxation was observed in wet swallowing, but not in dry swallowing. Furthermore, the extent of LES receptive relaxation induced by the first PWS (5.9 ± 2.05 mmHg) was much larger than that induced by the second PWS or later (1.73 ± 1.29 mmHg). After the first PWS, during repeated wet swallowing, LES pressure did not return to BLESP before starting the protocol. In contrast, there was no significant difference in the extent of swallow-induced LES relaxation between dry swallowing (13 ± 1.4 mmHg) and wet swallowing (11.4 ± 1.2 mmHg). Conclusion: Dry swallowing possesses only swallow-induced LES relaxation. Dry swallowing cannot achieve full EGJ relaxation, which is important for protecting against gastro-esophageal reflux. LES receptive relaxation is indispensable for successful EGJ relaxation in wet swallowing.

Figure 2. Receiver operating characteristic curves for high-resolution impedance manometry and timed barium esophagram measures to predict symptomatic outcomes. EII ratio, esophageal impedance integral; IBH, impedance bolus height; TBE, timed barium esophagram.

Sa1652 Sa1653 THE ASSOCIATION OF RADIOGRAPHIC AND HIGH-RESOLUTION IMPEDANCE MANOMETRY METRICS OF ESOPHAGEAL RETENTION WITH TREATMENT RESPONSE IN ACHALASIA Claire Beveridge, Dustin Carlson, Zhiyue Lin, Michelle Balla, Peter Kahrilas, John E. Pandolfino

ALTERED ESOPHAGEAL MECHANOSENSITIVITY OF SECONDARY PERISTALSIS AS A PATHOPHYSIOLOGICAL MARKER IN PATIENTS WITH GLOBUS SENSATION Chien-Lin Chen, Wei-Yi Lei, Jui-Sheng Hung, Chih-Hsun Yi, Fabio Pace, Tso-Tsai Liu Background/aim: Secondary peristalsis is important for clearance of retained food bolus and refluxate from the esophagus. Our prior work has demonstrated that globus patients are characterized with esophageal hypersensitivity with aberrant viscerosomatic referral (Gastroenterology 2008). Therefore, we aimed to investigate the hypothesis whether patients with globus sensation have altered physiological characteristics of esophageal distension-induced secondary peristalsis. Methods: After a baseline recording of primary peristalsis, secondary peristalsis was stimulated with slow and rapid mid-esophageal injections of air in 17 globus patients and 18 healthy controls. Distension thresholds and peristaltic activities of secondary peristalsis were analyzed and compared between the patients and healthy controls. Results:

Background: Post-treatment esophageal retention is frequently quantified in achalasia using timed barium esophagram (TBE) column height. However, TBE column area and novel high-resolution impedance manometry (HRIM) metrics have been proposed. We aim to evaluate the merit of TBE column area, esophageal impedance integral (EII) ratio, and impedance bolus height (IBH) as indicators of treatment response in achalasia. Methods: 70 patients (ages 20 - 81; 31 female) with achalasia were prospectively evaluated following pneumatic dilation or myotomy with Eckardt score, TBE, and HRIM. Eckardt scores ranged from 0 (asymptomatic) to 12; a score less than four was considered a good treatment outcome. TBE was assessed for column height and area 5 minutes after ingestion of 200

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The threshold volume for generating secondary peristalsis during slow air distension did not differ between the patient and control groups (p = 0.55). The threshold volume for generating secondary peristalsis during rapid air distension was significantly greater in patients with globus than healthy controls (7.0 ± 0.9 vs. 5.0 ± 0.3 mL, p = 0.04). Secondary peristalsis was trigged less frequently in globus patients as compared with healthy control after rapid air distension (40% [30-65%] vs. 60% [60-83%], p = 0.001). There was no difference in any of peristaltic parameters for primary and secondary peristalsis between the groups. Conclusions: There is a substantial defect in triggering of secondary peristalsis in patients with globus sensation, suggesting that altered mechanosensitivity to abrupt esophageal distension appears to an be a pathophysiological mechanism in globus sensation. Whether current findings could be a therapeutic target in the management of patients with globus sensation warrants further investigation.

Sa1654 INFLUENCE OF GABAB AGONIST BACLOFEN ON CAPSAICIN INDUCED EXCITATION OF ESOPHAGEAL SECONDARY PERISTALSIS IN HUMANS Chien-Lin Chen, Wei-Yi Lei, Jui-Sheng Hung, Tso-Tsai Liu, Chih-Hsun Yi Background/Aim: Secondary peristalsis is important for the clearance of retained refluxate or material from the esophagus. Esophageal instillation of capsaicin enhances secondary peristalsis. The gamma aminobutyric acid receptor type B (GABAB) agonist baclofen improves symptoms in patients with gastroesophageal reflux disease by direct inhibition of the gastroesophageal vagal tension mechanoreceptors. We aimed to investigate whether baclofen could influence heartburn perception and physiological alteration of secondary peristalsis subsequent to capsaicin infusion in healthy adults. Methods: Secondary peristalsis was induced by slow and rapid air mid-esophagus injections of air in 15 healthy subjects. Two different sessions including esophageal infusion of capsaicin-containing red pepper sauce (0.84 mg) following pretreatment with placebo or baclofen were randomly performed at least one week apart. Symptoms of heartburn, distension thresholds and secondary peristalsis were determined and compared between each study protocol. Results: The intensity of heartburn symptom subsequent to capsaicin infusion didn't differ between placebo and baclofen (P = 0.14). Baclofen significantly increased the threshold volume of secondary peristalsis to slow air injections subsequent to esophageal capsaicin infusion (14.7 ± 0.8 mL vs. 10.0 ± 0.5 mL; P < 0.001). Baclofen also significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal capsaicin infusion (7.2 ± 0.6 mL vs. 4.9 ± 0.4 mL; P = 0.002). The frequency of secondary peristalsis subsequent to acid infusion was significantly decreased after baclofen as compared to the placebo (50% [28−60%] vs. 80% [70−80%]; P < 0.001). Baclofen had no effect on any of peristaltic parameters of secondary peristalsis subsequent to capsaicin infusion during slow or rapid air injections. Conclusions: This study suggests that the GABAB agonist baclofen appears to desensitize the esophagus to capsaicin induced excitation of secondary peristalsis in health adults, which is probably mediated by both slowly adapting muscular and rapidly adapting mucosal mechanoreceptors. However, heartburn perception and secondary peristaltic characteristics subsequent to esophageal capsaicin infusion are not affected by baclofen.

Sa1656 ESOPHAGOGASTRIC JUNCTION OUTFLOW OBSTRUCTION IS DISCRIMINATED FROM ACHALASIA BY ESOPHAGEALLY EXPRESSED CYOTOKINE PROFILES USING LINEAR DISCRIMINANT ANALYSIS Yoshitaka Hata, Eikichi Ihara, Keita Fukaura, Kazumasa Muta, Xiaopeng Bai, Tsutomu Iwasa, Akira Aso, Hirotada Akiho, Kazuhiko Nakamura, Yoshihiro Ogawa Background: Based on the Chicago Classification, ver3.0, esophagogastric junction outflow obstruction disorders are classified into 4 phenotypes: achalasia (types I, II, and III) and esophagogastric junction outflow obstruction (EGJOO). Although EGJOO is considered to be a variant of achalasia, whether EGJOO is a precursor to achalasia or a disorder different from achalasia remains unclear. Objectives: This study was designed to determine how EGJOO is associated with achalasia in terms of esophageally expressed cytokine profiles. Patients and Methods: In total, 299 patients suspected to have an esophageal motility disorder were assessed by high-resolution manometry from May 2013 to October 2016. Among them, 10 patients with achalasia (type I, n=2; type II, n=6; type III, n=2), 10 with EGJOO, and 25 with normal high-resolution manometry findings were enrolled in this study. Biopsy samples were taken from the mucosa of the lower esophageal sphincter. Realtime reverse-transcription polymerase chain reaction was performed to assess the expression of T helper 1-related cytokines (tumor necrosis factor-α, interferon-γ, and interleukin [IL]1β), T helper 2-related cytokines (IL-4, IL-5, and IL-13), and T helper 17-related cytokines (IL-17A, IL-23, and IL-6). Data are expressed as mean ± standard error of the mean. Analysis of variance and linear discriminant analysis were performed. Results: The mean patient age was 58.7 ± 2.5 years. The mean basal lower esophageal sphincter pressure in the EGJOO, achalasia, and normal groups was 41.5 ± 17.0, 37.9 ± 14.0, and 27.7 ± 10.6 mmHg, respectively, and the mean integrated relaxation pressure was 21.5 ± 1.8, 30.2 ± 1.8, and 9.7 ± 1.2 mmHg, respectively (normal, <15 mmHg). The integrated relaxation pressure was significantly higher in the achalasia than EGJOO group. The mean distal contractile integral in the EGJOO and normal groups was 4774.0 ± 783.6 and 2089.4 ± 495.6 mmHg-cm-s, respectively. The distal contractile integral was significantly higher in the EGJOO than normal group. Analysis of variance showed that esophageal expression of tumor necrosis factor-a was significantly higher in the EGJOO group (but not in the achalasia group) than in the normal group, but there were no differences in the expression of any other cytokines among the normal, achalasia, and EGJOO groups. Linear discriminant analysis of the cytokine profiles in the three groups showed that the cytokine profile in the EGJOO group was clearly discriminated from that in the achalasia and normal groups, while the cytokine profiles were similar in the achalasia and normal groups (Fig. 1). A subanalysis showed that type III was discriminated from types I/II and that type I differed most from EGJOO. Conclusions: EGJOO has different cytokine profiles from those of achalasia. EGJOO could be a disorder different from achalasia.

Sa1655 BODY MASS INDEX, ESOPHAGEAL DYSMOTILITY, AND GASTROESOPHAGEAL REFLUX DISEASE. IS THERE A RELATIONSHIP? Caroline E. Sheppard, Daniel C. Sadowski, Christopher J. de Gara, Daniel W. Birch Introduction Obesity is identified as a risk factor for gastroesophageal reflux disease. The purported mechanisms are commonly thought to be increased intraabdominal pressure (IAP), increased intragastric pressure (IGP) and resulting esophagogastric junction (EGJ) disruption. Esophageal motility disorders are also a risk factor for reflux. However, the impact that obesity has on esophageal motility is not clear and has mostly been explored in the selective bariatric population. Aim The objective of this study was to quantify the relationship between obesity, gastroesophageal reflux and esophageal motility in a population requiring investigations for esophageal symptoms. Methods Patient data was prospectively collected over an 18-month period. A total of 1602 patients underwent ambulatory 24h pH/impedance (ApHI) testing and/or high resolution esophageal manometry (EM). Patients with previous gastric surgery or on anti-secretory therapy during the study were excluded. IAP was approximated by measuring IGP during basal conditions, 5cm below the lower esophageal sphincter (LES) margin. A linear multivariate regression model was used to explore DeMeester score. A logistic multivariate regression was used to identify predictors of reflux and abnormal esophageal motility. Results A total of 333 patients underwent both EM and ApHI testing off anti-secretory therapy. Patients had an average BMI of 29.3±6.1kg/m2 (15.9-59.0kg/m2). The median DeMeester score was 12.4 (0.8-133.9). 42% had pathological reflux. Linear regression found presence of heartburn(p=0.002) and regurgitation symptoms(p=0.003), decreased LES pressure(p<0.001), and higher BMI(p=0.012) were associated with DeMeester score. However, BMI appeared to have a logarithmic rather than linear relationship with DeMeester after stratifying BMI into WHO's 6 BMI categories (Figure 1). The logistic regression identified the presence and size of a hiatal hernia (OR:2.5, 95%CI 1.4-4.5, p=0.001) as an additional significant predictor of reflux. A total of 1319 patients underwent EM. Average patient age was 54.1±15.0years. 52% had abnormal results, most frequently ineffective esophageal motility (24%) and EGJ outflow obstruction (14%). Older(p<0.001) patients with dysphagia symptoms(p<0.001), no heartburn symptoms(p=0.008), and lower BMI(p=0.037) were at greater risk of abnormal esophageal motility. Reflux was not a predictor of dysmotility(p=0.8). There was a positive linear association between BMI and IGP(p<0.001). However, no significant relationship existed between IGP and DeMeester score(p=0.6) (Figure 2) or LES pressure(p=0.6). Conclusions As a stand-alone factor a relationship between BMI and reflux does exist. However, the relationship does not appear to be the linear relationship other studies have reported. Further evaluation of the contradictory relationship between esophageal motility and BMI is required.

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