Short-term results of laparoscopic anti-reflux surgery with the RefluxStop device in patients with gastro-esophageal reflux disease and ineffective esophageal motility.

PURPOSE: In gastro-esophageal reflux disease (GERD) requiring surgical treatment, concomitant ineffective esophageal motility (IEM) is a decisive factor in surgical planning, due to concern regarding dysphagia. Anti-reflux surgery with the RefluxStop device is a promising technique. We assessed initial feasibility and clinical outcomes of RefluxStop surgery in patients with GERD and IEM. METHODS: Retrospective analysis of patients with GERD, hiatal hernia (HH), and IEM, who underwent surgery with RefluxStop at our institution and achieved 12-month follow-up. Technique feasibility was assessed, in addition to symptom resolution (GERD-HRQL questionnaire), adverse events, HH recurrence, dysphagia, and patient satisfaction. Placement of the device was confirmed by video fluoroscopy on postoperative day 1, and at 3 and 12 months. RESULTS: Between June 2020 and November 2022, 20 patients with IEM underwent surgery with RefluxStop and completed 12-month follow-up. All patients reported typical symptoms of GERD, and 12 had preoperative dysphagia. The median HH length was 4.5 cm (IQR, 3.75-5). The median operating time was 59.5 min (IQR, 50.25-64) with no implant-related intra- or postoperative complications. No HH recurrence was observed. One patient reported persistent left-sided thoracic pain at 11 months post-surgery, which required diagnostic laparoscopy and adhesiolysis. Three patients reported severe postoperative dysphagia: balloon dilatation was performed towards resolution. The mean GERD-HRQL scores improved (from 40.7 at baseline to 4.8 at 3 months and 5.7 at 12 months (p <0.001)). CONCLUSION: RefluxStop surgery was feasible and offered effective treatment for this group of patients with GERD and IEM. All patients had complete resolution or significant improvement of GERD symptoms, and 90% of them were satisfied with their quality of life 1 year after surgery.

Comparative Prevalence of Ineffective Esophageal Motility: Impact of Chicago v4.0 vs. v3.0 Criteria.

Background and Objectives: The threshold for ineffective esophageal motility (IEM) diagnosis was changed in Chicago v4.0. Our aim was to determine IEM prevalence using the new criteria and the differences between patients with definite IEM versus "inconclusive diagnosis". Materials and Methods: We retrospectively selected IEM and fragmented peristalsis (FP) patients from the high-resolution esophageal manometries (HREMs) database. Clinical, demographic data and manometric parameters were recorded. Results: Of 348 HREMs analyzed using Chicago v3.0, 12.3% of patients had IEM and 0.86% had FP. Using Chicago v4.0, 8.9% of patients had IEM (IEM-4 group). We compared them with the remaining 16 with an inconclusive diagnosis of IEM (borderline group). Dysphagia (77% vs. 44%, Z-test = 2.3, p = 0.02) and weight loss were more commonly observed in IEM-4 compared to the borderline group. The reflux symptoms were more prevalent in the borderline group (87.5% vs. 70.9%, p = 0.2). Type 2 or 3 esophagogastric junction morphology was more prevalent in the borderline group (81.2%) vs. 64.5% in IEM-4 (p = 0.23). Distal contractile integral (DCI) was lower in IEM-4 vs. the borderline group, and resting lower esophageal sphincter (LES) pressure and mean integrated relaxation pressure (IRP) were similar. The number of ineffective swallows and failed swallows was higher in IEM-4 compared to the borderline group. Conclusions: Using Chicago v4.0, less than 10% of patients had a definite diagnosis of IEM. The dominant symptom was dysphagia. Only DCI and the number of failed and inefficient swallows were different between definite IEM patients and borderline cases.

Esophageal Motility Disorders: Current Approach to Diagnostics and Therapeutics.

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.

Acute transcutaneous electrical stimulation (TES) augments esophageal contractility in patients with weak peristalsis.

BACKGROUND: Lung transplantation (LTx) remains controversial in patients with absent peristalsis (AP) given the increased risk for gastroesophageal reflux (GER), and chronic lung allograft dysfunction. Furthermore, specific treatments to facilitate LTx in those with AP have not been widely described. Transcutaneous Electrical Stimulation (TES) has been reported to improve foregut contractility in LTx patients and therefore we hypothesize that TES may augment the esophageal motility of patients with ineffective esophageal motility (IEM). METHODS: We included 49 patients, 14 with IEM, 5 with AP, and 30 with normal motility. All subjects underwent standard high-resolution manometry and intraluminal impedance (HRIM) with additional swallows as TES was delivered. RESULTS: TES induced a universal impedance change observable in real-time by a characteristic spike activity. TES significantly augmented the contractile vigor of the esophagus measured by the distal contractile integral (DCI) in patients with IEM [median DCI (IQR) 0 (238) mmHg-cm-s off TES vs. 333 (858) mmHg-cm-s on TES; p = .01] and normal peristalsis [median DCI (IQR) 1545 (1840) mmHg-cm-s off TES vs. 2109 (2082) mmHg-cm-s on TES; p = .01]. Interestingly, TES induced measurable contractile activity (DCI > 100 mmHg-cm-s) in three out of five patients with AP [median DCI (IQR) 0 (0) mmHg-cm-s off TES vs. 0 (182) mmHg-cm-s on TES; p < .001]. CONCLUSION: TES acutely augmented contractile vigor in patients with normal and weak/ AP. The use of TES may positively impact LTx candidacy, and outcomes for patients with IEM/AP. Nevertheless, further studies are needed to determine the long-term effects of TES in this patient population.

Chicago Classification Version 4.0 Improves Stratification of Ineffective Esophageal Motility Patients into Clinically Meaningful Subtypes: A Two-Center International Study.

The 4th iteration of the Chicago Classification (CC v4.0) for esophageal motility disorders offers more restrictive criteria for the diagnosis of Ineffective Esophageal Motility (IEM) compared to version 3.0 (CC v3.0). In light of the updated criteria for IEM, we aimed to characterize and compare the patients who retained their IEM diagnosis to those who were reclassified as normal motility, and to evaluate the clinical impact of the newly introduced CC v4.0. We performed a retrospective case-control study. We included all individuals who underwent a high-resolution manometry (HRM) between 2020 and 2021 at two centers. Consecutive studies reported as IEM according to the CC v3.0 were reanalyzed according to the CC v4.0. We compared demographics, clinical, manometry, and pH-monitoring parameters. Out of 452 manometry studies, 154 (34%) met criteria for IEM as per the CC v3.0 (CC v3.0 IEM group). Of those, 39 (25%) studies were reclassified as normal studies according to the CC v4.0 (CC v4.0 normal group), while the remaining 115 studies (25% of the overall cohort) retained an IEM diagnosis (CC v4.0 IEM group). The CC v4.0 normal group had more recovered contractions during solid swallows (p = 0.01), less ineffective swallows (p = 0.04), and lower acid exposure time (p = 0.02) compared to the CC4.0 IEM group. Under CC v4.0 criteria, fewer patients are diagnosed with IEM. Those diagnosed with IEM had worse esophageal function and higher acid burden. Though further studies are needed to confirm these findings, our results indicate that CC v4.0 criteria restrict the IEM diagnosis to a more clinically meaningful population.

Ineffective esophageal motility is not a contraindication to total fundoplication.

INTRODUCTION: Ineffective esophageal motility (IEM) is a physiologic diagnosis and is a component of the Chicago Classification. It has a strong association with gastroesophageal reflux and may be found during work-up for anti-reflux surgery. IEM implies a higher risk of post-op dysphagia if a total fundoplication is done. We hypothesized that IEM is not predictive of dysphagia following fundoplication and that it is safe to perform total fundoplication in appropriately selected patients. METHODS: Retrospective chart review of patients who underwent total fundoplication between September 2012 and December 2018 in a single foregut surgery center and who had IEM on preoperative manometry. We excluded patients who had partial fundoplication, previous foregut surgery, other causes of dysphagia or an esophageal lengthening procedure. Dysphagia was assessed using standardized Dakkak score ≤ 40 and GERD-HRQL question 7 ≥ 3. RESULTS: Two hundred patients were diagnosed with IEM and 31 met the inclusion criteria. Median follow-up: 706 days (IQR 278-1348 days). No preoperative factors, including subjective dysphagia, transit on barium swallow, or individual components of manometry showed statistical correlation with postoperative dysphagia. Of 9 patients with preoperative dysphagia, 2 (22%) had persistent postoperative dysphagia and 7 had resolution. Of 22 patients without preoperative dysphagia, 3 (14%) developed postoperative dysphagia; for a combined rate of 16%. No patient needed re-intervention beyond early recovery or required reoperation for dysphagia during the follow-up period. CONCLUSION: In appropriately selected patients, when total fundoplication is performed in the presence of preoperative IEM, the rate of long-term postoperative dysphagia is similar to the reported rate of dysphagia without IEM. With appropriate patient selection, total fundoplication may be performed in patients with IEM without a disproportionate increase in postoperative dysphagia. The presence of preoperative IEM should not be rigidly applied as a contraindication to a total fundoplication.

Effect of electrical stimulation therapy of the lower esophageal sphincter in GERD patients with ineffective esophageal motility.

BACKGROUND: Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) is a novel technique in antireflux surgery. Due to the minimal alteration at the LES during surgery, LES-EST is meant to be ideal for patients with gastroesophageal reflux disease (GERD) and ineffective esophageal motility (IEM). The aim of this prospective trial (NCT03476265) is to evaluate health-related quality of life and esophageal acid exposure after LES-EST in patients with GERD and IEM. METHODS: This is a prospective non-randomized open-label study. Patients with GERD and IEM undergoing LES-EST were included. Follow-up (FUP) at 12 months after surgery included health-related quality of life (HRQL) assessment with standardized questionnaires (GERD-HRQL) and esophageal functional testing. RESULTS: According to the study protocol, 17 patients fulfilled eligibility criteria. HRQL score for heartburn and regurgitation improved from 21 (interquartile range (IQR) 15-27) to 7.5 (1.25-19), p = 0.001 and from 17 (11-23.5) to 4 (0-12), p = 0.003, respectively. There was neither significant improvement of esophageal acid exposure nor reduction of number of reflux events in pH impedance measurement. Distal contractile integral improved from 64 (11.5-301) to 115 (IQR 10-363) mmHg s cm, p = 0.249. None of the patients showed any sign of dysphagia after LES-EST. One patient needed re-do surgery and re-implantation of the LES-EST due to breaking of the lead after one year. CONCLUSION: Although patient satisfaction improved significantly after surgery, this study fails to demonstrate normalization or significant improvement of acid exposure in the distal esophagus after LES-EST.

Patients with ineffective esophageal motility benefit from laparoscopic antireflux surgery.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common chronic disorder of the gastrointestinal tract, affecting more than 50% of Americans. The development of GERD may be associated with ineffective esophageal motility (IEM). The impact of esophageal motility on outcomes post laparoscopic antireflux surgery (LARS), including quality of life (QOL), remains to be defined. The purpose of this study is to analyze and compare QOL outcomes following LARS among patients with and without ineffective esophageal motility (IEM). METHODS: This is a single-institution, retrospective review of a prospectively maintained database of patients who underwent LARS, from January 2012 to July 2019, for treatment of GERD at our institution. Patients undergoing revisional surgery were excluded. Patients with normal peristalsis (non-IEM) were distinguished from those with IEM, defined using the Chicago classification, on manometric studies. Four validated QOL surveys were used to assess outcomes: Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Health-Related QOL (GERD-HRQL), Laryngopharyngeal Reflux Health-Related QOL (LPR-HRQL), and Swallowing Disorders (SWAL) survey. RESULTS: 203 patients with complete manometric data were identified (75.4% female) and divided into two groups, IEM (n = 44) and non-IEM (n = 159). IEM and Non-IEM groups were parallel in age (58.1 ± 15.3 vs. 62.2 ± 12 years, p = 0.062), body mass index (27.4 ± 4.1 vs. 28.2 ± 4.9 kg/m2, p = 0.288), distribution of comorbid disease, sex, and ASA scores. The groups differed in manometry findings and Johnson-DeMeester score (IEM: 38.6 vs. Non-IEM: 24.0, p = 0.023). Patients in both groups underwent similar rates of Nissen fundoplication (IEM: 84.1% vs. Non-IEM: 93.7%, p = 0.061) with greater improvements in dysphagia (IEM: 27.4% vs. 44.2%) in Non-IEM group but comparable benefit in reflux reduction (IEM: 80.6% vs. 72.4%) in both groups at follow-up. There were no differences in postoperative outcomes. Satisfaction rates with LARS were similar between groups (IEM: 80% vs. non-IEM: 77.9%, p > 0.05). CONCLUSION: Patients with ineffective esophageal motility derive significant benefits in perioperative and QOL outcomes after LARS. Nevertheless, as anticipated, their baseline dysmotility may reduce the degree of improvement in dysphagia rates post-surgery compared to patients with normal motility. Furthermore, the presence of preoperative IEM should not be a contraindication for complete fundoplication. Key to optimal outcomes after LARS is careful patient selection based on objective perioperative data, including manometry evaluation, with the purpose of tailoring surgery to provide effective reflux control and improved esophageal clearance.

Pressure-impedance analysis: Assist the diagnosis and classification of ineffective esophageal motility disorder.

BACKGROUND AND AIM: We elucidated the clinical significance of distal contractile integral-to-esophageal impedance integral (EII) ratio (DCIIR) in ineffective esophageal motility (IEM) adult patients. METHODS: We recruited 101 patients with IEM (48.38 ± 1.58 years) and 42 matched healthy volunteers (44.28 ± 1.85 years) in this case-control study. All subjects underwent esophageal high-resolution impedance manometry from October 2014 to May 2018. The diagnosis of IEM was based on the Chicago Classification version 3.0. The EII, EII ratio, and DCIIR were analyzed by matlab software. RESULTS: The EII, EII ratio, and DCIIR calculated at an impedance threshold of 1500 Ω (EII1500, EII ratio1500, and DCIIR1500, respectively) were significantly lower in the IEM group than in healthy controls (P < 0.0001, < 0.0001, and < 0.0001, respectively). Receiver operating characteristic analysis showed that DCIIR1500 < 0.008 mmHg/Ω, EII1500 > 71 000 Ω.s.cm, and EII ratio1500 > 0.43 were all predictive of IEM. Only DCIIR1500 < 0.008 mmHg/Ω remained significant in diagnosing IEM in the multivariate logistic regression analysis (odds ratio = 72.13, P < 0.001). The DCIIR1500 is negatively correlated with Eckardt score and the Reflux Disease Questionnaire (correlation coefficient = -0.2844 and -0.3136; P = 0.0006 and 0.0002, respectively). Receiver operating characteristic analysis further showed that a DCIIR1500 cut-off of 0.002 mmHg/Ω achieved the best differentiation between the IEM-alternans and IEM-persistens subtypes among IEM patients (P < 0.001). CONCLUSIONS: The novel pressure-impedance parameter of high-resolution impedance manometry, DCIIR1500, may assist in the diagnosis and classification of IEM and correlated with clinical symptoms.

Impact of ineffective esophageal motility on chemical clearance in patients with gastroesophageal reflux symptoms.

Ineffective esophageal motility (IEM) is the most common manometric abnormality in gastroesophageal reflux disease (GERD). However, the impact of IEM on esophageal chemical clearance has not been fully investigated. This study aimed to determine the impact of IEM on esophageal chemical clearance in patients with GERD. A total of 369 patients with GERD symptoms who underwent upper endoscopy and high-resolution manometry (HRM) test were retrospectively analyzed. The relationship between IEM and erosive esophagitis was examined. In addition, the impact of IEM on chemical clearance was examined in patients who underwent an additional combined multichannel intraluminal impedance-pH (MII-pH) test. Esophageal chemical clearance capability was evaluated via postreflux swallow-induced peristaltic wave (PSPW) index and acid clearance time (ACT). Of 369 patients, 181 (49.1%) had esophageal motility disorders, of which 78 (21.1%) had IEM. The proportion of IEM patients in those with erosive esophagitis and those without were 16.2% and 21.7%, respectively, and no significant difference was observed (P = 0.53). After excluding patients other than those with IEM and normal esophageal motility, 64 subsequently underwent MII-pH test. The median values of the PSPW index in the IEM and normal esophageal motility group were 11.1% (4.2%-20.0%) and 17.1% (9.8%-30.6%), respectively. The PSPW index was significantly lower in the IEM group than in the normal esophageal motility group (P < 0.05). The median ACT values in the IEM group and normal esophageal motility group were 125.5 (54.0-183.5) seconds and 60.0 (27.2-105.7) seconds, respectively. The ACT was significantly longer in the IEM group than in the normal esophageal motility group (P < 0.05). In conclusion, IEM was found to be associated with chemical clearance dysfunction as measured against the PSPW index and ACT. As this condition could be a risk factor for GERD, future treatments should be developed with a focus on chemical clearance.

Ineffective Esophageal Motility Is Associated with Impaired Bolus Clearance but Does Not Correlate with Severity of Dysphagia.

BACKGROUND: Ineffective esophageal motility (IEM) is defined as a distal contractile integral < 450 mmHg/s/cm in at least 50% of ten liquid swallows on high-resolution esophageal manometry (HREM). Whether this latest definition correlates with degree of symptoms has not been studied. METHODS: Patients presenting for HREM prospectively rated their symptoms using the Eckardt score. Topography plots were retrospectively reviewed and classified according to the latest Chicago Classification. Patients with non-obstructive dysphagia and an Eckardt score of at least 1 were included. Patients with major motility disorders were excluded. Scores between patients with IEM (group A) and patients with normal classification (group B) were compared using two-tailed t-tests. Spearman's correlation coefficient was calculated to determine correlation between symptoms and percent bolus clearance. RESULTS: A total of 241 patients were screened; 33 patients met criteria for group A and 44 patients for group B. There was no difference between the two groups in mean symptom severity for dysphagia (1.63 vs. 1.61, P = 0.89), chest pain (0.67 vs. 0.75, P = 0.64), regurgitation (1.06 vs. 0.85, P = 0.32), or weight loss (0.85 vs. 0.49, P = 0.11). The percent bolus clearance was significantly lower in group A (46.5% vs. 76.7%, P > 0.01). There was a moderate inverse correlation between dysphagia and percent bolus clearance (R = - 0.37) in group A, but none in group B (R = 0.09). CONCLUSION: The classification of IEM did not discriminate from normal studies for symptom severity in our cohort. However, patients with IEM did have an inverse correlation between dysphagia score and bolus clearance, but those without IEM did not. Adding impedance information to the motor pattern classification should be considered in the symptom assessment in minor motility disorders.

Electrical lower esophageal sphincter augmentation in patients with GERD and severe ineffective esophageal motility-a safety and efficacy study.

BACKGROUND: Laparoscopic fundoplication (LF), even if performed in specialized centers, can be followed by long-term side effects such as dysphagia, gas bloating or inability to belch. Patients with an ineffective esophageal motility (IEM) and concurrent GERD are prone to postoperative dysphagia after LF. The aim of this study is to evaluate the safety and efficacy of electrical lower esophageal sphincter stimulation in patients with IEM and GERD. METHODS: This is a prospective, open-label single center study. Patients with PPI-refractory GERD and ineffective esophageal motility were included for lower esophageal sphincter electrical stimulation (LES-EST). Patients underwent prospective follow-up including physical examination, interrogation of the device and were surveyed for changes in the health-related quality of life score. RESULTS: According to power analysis, 17 patients were included in this study. Median distal contractile integral (DCI) was 64 mmHg s cm (quartiles 11.5-301). Median total % pH < 4 was 8.9 (quartiles 4-21.6). Twelve patients (70.6%) underwent additional hiatal repair. At 1-month follow-up, none of the patients showed any clinical or radiological signs of dysphagia. There were no procedure related severe adverse events. Mean total HQRL improved from baseline 37.53 (SD 15.07) to 10.93 (SD 9.18) at follow-up (FUP) (mean difference 24.0 CI 15.93-32.07) p < 0.001. CONCLUSIONS: LES-EST was introduced as a potential technique to avoid side effects of LF. LES-EST significantly improved health related quality of life and does not impair swallowing in patients with GERD and ineffective esophageal motility.

Role of esophageal manometry in children with refractory gastroesophageal reflux symptoms.

BACKGROUND: We investigated the prevalence of psychiatric referral, frequency of repeat upper gastrointestinal (UGI) contrast studies, and esophagogastroduodenoscopy (EGD) in children with ineffective esophageal motility (IEM) before the confirmation of esophageal dysmotility. METHODS: A total of 19 children (nine boys, 10 girls; mean age, 13.80 ± 5.10 years) with symptoms of refractory gastroesophageal reflux (GER) who underwent high-resolution esophageal impedance manometry (HRIM) were enrolled in this retrospective analysis. Refractory GER symptoms were defined as persistent symptoms even under acid-suppression therapy for 8 weeks in this study. Clinical data including age, gender, time from symptom onset to diagnosis, and number of UGI contrast studies and EGD before diagnosis were obtained. HRM parameters and the prevalence of psychiatric referral were also analyzed. RESULTS: There are 14 children (73.68%) diagnosed with IEM by HRIM, and another 5 children (26.32%) diagnosed as GER disease (GERD) by EGD. A significant proportion of IEM children were misdiagnosed with psychological problems compared with the GERD children (78.57% vs 20.00%, P = 0.04). Three IEM children (21.43%) received antipsychotic and antidepressant agents before diagnosis of IEM, and all of them discontinued these medications after diagnosis. IEM children underwent a greater number of UGI contrast studies (1.07 ± 0.92 vs 0.20 ± 0.45; P = 0.02) and EGD (2.36 ± 2.50 vs 0.60 ± 0.55; P = 0.03) before HRM than GERD children. CONCLUSIONS: Esophageal manometry for the diagnosis of IEM should be considered in children with GER symptoms refractory to acid-suppression therapy for 8 weeks to avoid repeat UGI contrast studies, EGD, and psychological therapy.

Influence of prucalopride on esophageal secondary peristalsis in reflux patients with ineffective motility.

BACKGROUND AND AIM: Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary peristalsis by stimulating 5-hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM. METHODS: After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid-esophageal injections of air in 15 patients with IEM. Two separate sessions with 4-mg oral prucalopride or placebo were randomly performed. RESULTS: Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% [43-70%]) than placebo (45% [33-50%]) (P = 0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs 69.5 ± 12.9 mmHg; P = 0.09). CONCLUSIONS: Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.

The Effect of Ineffective Esophageal Motility on Gastroesophageal Reflux Disease.

BACKGROUND/AIMS: Ineffective esophageal motility (IEM) is the most common gastrointestinal motility disorder. Studies have reported that IEM is related to gastroesophageal reflux disease (GERD). However, the relationship between IEM and GERD remains uncertain. This study aims to clarify this relationship retrospectively. METHODS: We analyzed 195 subjects who underwent high-resolution manometry between January 2011 and September 2016. Of these subjects, 72 had normal esophageal motility (NEM) and 26 had IEM. We investigated differences in the clinical characteristics, severity and duration of GERD symptoms, and comorbid extra-esophageal symptoms of the subjects. Comorbid extra-esophageal symptoms were assessed with the Gastrointestinal Symptom Rating Scale questionnaire. Investigation-defined GERD was diagnosed when erosive esophagitis or abnormal multichannel intraluminal impedance was present. RESULTS: We found no significant difference in the prevalence of IEM between patients with and without GERD (37.5 and 21.1%, respectively; p = 0.174). There were no differences in age, gender, body mass index, presence of hiatal hernia, or duration of GERD between the groups. Compared to patients with NEM, those with IEM were significantly less likely to have comorbid extra-esophageal symptoms (p < 0.05). CONCLUSION: There is no association between IEM and GERD.

Ineffective Esophageal Motility (IEM): the Old-New Frontier in Esophagology.

Ineffective esophageal motility (IEM) is characterized by distal esophageal contraction amplitude of <30 mmHg on conventional manometry (Blonski et al. Am J Gastroenterol. 103(3):699-704, 2008), or a distal contractile integral (DCI) < 450 mmHg*s*cm on high-resolution manometry (HRM) (Kahrilas et al. Neurogastroenterol Motil. 27(2):160-74, 2015) in≥50 % of test swallows. IEM is the most common abnormality on esophageal manometry, with an estimated prevalence of 20-30 % (Tutuian and Castell Am J Gastroenterol. 99(6):1011-9, 2004; Conchillo et al. Am J Gastroenterol. 100(12):2624-32, 2005). Non-obstructive dysphagia has been considered to be frequently associated with severe esophageal peristaltic dysfunction. Defective bolus transit (DBT) on multichannel intraluminal impedance testing was found in more than half of IEM patients who presented with dysphagia (Tutuian and Castell Am J Gastroenterol. 99(6):1011-9, 2004), highlighting the functional defect of this manometric finding. Treatment of IEM has been challenging because of lack of promotility agents that have a definite effect on esophageal function.

Relevance of ineffective esophageal motility to secondary peristalsis in patients with gastroesophageal reflux disease.

BACKGROUND AND AIMS: The study aimed to investigate the hypothesis whether the presence of Ineffective esophageal motility would affect physiological characteristics of secondary peristalsis. METHODS: Secondary peristalsis was performed with slow and rapid air injections into mid-esophagus of 18 ineffective esophageal motility patients and 15 age-matched controls. Severity of ineffective esophageal motility was defined by the application of combined multichannel intraluminal impedance and manometry. RESULTS: Ineffective esophageal motility patients included 11 patients without impedance abnormality and seven patients with impedance abnormality during liquid and/or viscous swallowing. The prevalence of failed secondary peristaltic response during slow air injection was significantly greater in ineffective esophageal motility patients without impedance abnormality (3/11 [27%], P < 0.001) and with impedance abnormality (4/7 [57%], P = 0.04) than healthy subjects. The threshold volume for inducing secondary peristalsis during rapid air injection was significantly greater in ineffective esophageal motility patients with impedance abnormality (6.1 ± 0.3 mL) than healthy subjects (4.6 ± 0.3 mL, P < 0.05) and ineffective esophageal motility patients without impedance abnormality (4.1 ± 0.4 mL, P < 0.05). The frequency of peristaltic response during rapid air injection was significantly lower in ineffective esophageal motility patients with impedance abnormality (40% [20-50%] than healthy subjects (90% [90-100%], P < 0.05). CONCLUSIONS: Defective activation of secondary peristalsis is present in ineffective esophageal motility patients with impedance abnormality. Our study indicates that increased ineffective esophageal motility severity associated with defective triggering of secondary peristalsis may contribute to impaired esophageal clearance in patients with gastroesophageal reflux disease.

Relevance of ineffective esophageal motility to striated esophageal muscle contraction: Studies with high-resolution manometry.

Striated esophageal muscle contraction (SEC) is important for pharyngeal swallowing and deglutition augmentation against aspiration. Its clinical relevance is unclear in patients with ineffective esophageal motility (IEM). In this study, we aimed to characterize and compare SEC in consecutive patients with and without IEM. All eligible patients were evaluated for SEC, primary and secondary peristalsis using high-resolution manometry (HRM) with one mid-esophageal injection port. Primary peristalsis was assessed with 10 5-mL liquid swallows and multiple rapid swallows (MRS), while secondary peristalsis was performed with rapid air injections of 20 mL. All peristatic parameters of HRM were measured, and SEC and its contractile integral (SECI) were evaluated. One hundred and forty patients (59.3% women, mean age 46.1 ± 13.1 years) were included. There was no difference in SECI between patients with and without IEM (p = 0.91). SECI was also similar between patients with and without secondary peristalsis for IEM (p = 0.63) or normal motility (p = 0.80). No difference in SECI was seen between patients with and without MRS for IEM (p = 0.55) or normal motility (p = 0.88). SECI was significantly higher in male patients than female patients in IEM patients (p = 0.01). SECI significantly correlated with age in patients with normal motility (r = -0.31, p = 0.01). Aging may have a negative impact on SEC in patients with normal motility, while gender difference in SECI occurs in IEM patients. Neither secondary peristalsis nor MRS influences SECI.

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.