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Our prior study reveals that the distension-contraction profiles using high-resolution manometry impedance recordings can distinguish patients with dysphagia symptom but normal esophageal function testing ("functional dysphagia") from control subjects. The aim of this study was to determine the diagnostic value of the recording protocol used in our prior studies (10-mL swallows with subjects in the Trendelenburg position) against the standard clinical protocol (5-mL swallows with subjects in the supine position). We used advanced machine learning techniques and robust metrics for classification purposes. Studies were performed on 30 healthy subjects and 30 patients with functional dysphagia. A custom-built software was used to extract the relevant distension-contraction features of esophageal peristalsis. Ensemble methods, i.e., gradient boost, support vector machines (SVMs), and logit boost, were used as the primary machine learning algorithms. Although the individual contraction features were marginally different between the two groups, the distension features of peristalsis were significantly different. The receiver operating characteristic (ROC) curve values for the standard recording protocol and the distension features ranged from 0.74 to 0.82; they were significantly better for the protocol used in our prior studies, ranging from 0.81 to 0.91. The ROC curve values using three machine learning algorithms were far superior for the distension than the contraction features of esophageal peristalsis, revealing a value of 0.95 for the SVM algorithm. Current patient classification for esophageal motility disorders, based on the contraction phase of peristalsis, ignores a large number of patients who have an abnormality in the distension phase of peristalsis. Distension-contraction plots should be the standard for assessing esophageal peristalsis in clinical practice. NEW & NOTEWORTHY Our findings underscore the superiority of distension features over contraction metrics in diagnosing esophageal dysfunctions. By leveraging state-of-the-art machine learning techniques, our study highlights the diagnostic potential of distension-contraction plots of peristalsis. Implementation of these plots could significantly enhance the accuracy of identifying patients with esophageal motor disorders, advocating for their adoption as the standard in clinical practice.

Background: Age-related changes in the gastrointestinal system are common and may be influenced by physiological aging processes. To date, a comprehensive analysis of esophageal motor disorders in patients belonging to various age groups has not been adequately reported., Methods: We conducted a retrospective assessment of high-resolution manometry (HRM) studies in a multicenter setting. HRM parameters were evaluated according to the Chicago Classification version 4.0. Epidemiological, demographic, clinical data, and main manometric parameters, were collected at the time of the examination. Age groups were categorized as early adulthood (<35 years), early middle-age (35-49 years), late middle-age (50-64 years), and late adulthood (≥65 years)., Results: Overall, 1341 patients (632, 47.0% male) were included with a median age of 55 years. Late adulthood patients reported more frequently dysphagia (35.2%) than early adulthood patients (24.0%, p = 0.035), early middle-age patients (21.0%, p < 0.0001), and late middle-aged patients (22.7%, p < 0.0001). Esophagogastric junction outflow obstruction was more prevalent in late adulthood (16.7%) than in early adulthood (6.1%, p = 0.003), and in early middle-age (8.1%, p = 0.001). Patients with normal esophageal motility were significantly younger (52.0 years) than patients with hypercontractile esophagus (61.5 years), type III achalasia (59.6 years), esophagogastric junction outflow obstruction (59.4 years), absent contractility (57.2 years), and distal esophageal spasm (57.0 years), in multivariate model (p < 0.0001)., Conclusion: The rate of esophageal motor disorders is higher in older patients, in particular esophagogastric junction outflow obstruction and hypercontractile esophagus. Future prospective studies are necessary to confirm our results and to find tailored strategies to improve clinical outcomes., (© 2024 The American Geriatrics Society.)

Background and Purpose: Ineffective esophageal motility (IEM) is the most frequently diagnosed esophageal motility abnormality and characterized by diminished esophageal peristaltic vigor and frequent weak, absent, and/or fragmented peristalsis on high-resolution esophageal manometry. Despite its commonplace occurrence, this condition can often provoke uncertainty for both patients and clinicians. Although the diagnostic criteria used to define this condition has generally become more stringent over time, it is unclear whether the updated criteria result in a more precise clinical diagnosis. While IEM is often implicated with symptoms of dysphagia and gastroesophageal reflux disease, the strength of these associations remains unclear. In this review, we share a practical approach to IEM highlighting its definition and evolution over time, commonly associated clinical symptoms, and important management and treatment considerations. We also share the significance of this condition in patients undergoing evaluation for anti-reflux surgery and consideration for lung transplantation., (© 2024 John Wiley & Sons Ltd.)

Background: Esophagogastric junction outflow obstruction (EGJOO) is a heterogenous disorder in which the correct management strategy is unclear. We assessed whether functional lumen imaging probe (FLIP) topography data could select EGJOO, which would benefit from lower esophageal sphincter Botulinum toxin (Botox) injection., Methods: This was a single-center prospective study of adult patients meeting Chicago Classification (CC) v3.0 criteria for EGJOO. We assessed differences in pretreatment physiologic measurements on high-resolution manometry (HRM) and FLIP and other relevant clinical variables in predicting Botox response (>50% in BEDQ at 2 months)., Key Results: Sixty-nine patients were included (ages 33-90, 73.9% female). Of these, 42 (61%) were Botox responders. Majority of physiologic measures on HRM and FLIP and esophageal emptying were not different based on Botox response. However, a spastic-reactive (SR) FLIP contractile response (CR) pattern predicted a Botox response with OR 25.6 (CI 2.9-229.6) when compared to antegrade FLIP CR; and OR for impaired-disordered/absent CR was 22.5 (CI 2.5-206.7). Logistic regression model using backward elimination (p value = 0.0001, AUC 0.79) showed that a SRCR or IDCR/absent response and the upright IRP predicted Botox response. Response rates in tiered diagnostic groups were: (i) CCv3.0 EGJOO (60.9%), (ii) CCv4.0 EGJOO (73.1%), (iii) CCv4.0 + FLIP REO (80%), (iv) CCv4.0, FLIP REO, and abnormal FLIP CR (84.2%), and (v) CCv4.0, FLIP REO, and SR FLIP CR (90%)., Conclusions and Inferences: FLIP helps identify patients with EGJOO who are likely to response to LES Botox therapy. An abnormal FLIP contractile response pattern is the single-most important predictor of a Botox response., (© 2024 John Wiley & Sons Ltd.)

Non-achalasia oesophageal motility disorders (NAOMD) represent a heterogeneous group of rare diseases, including oesophagogastric junction outflow obstruction, distal oesophageal spasm, and hypercontractile oesophagus. Despite the differing aetiological, manometric and pathophysiological characteristics, these disorders are unified by similar clinical presentation, including dysphagia and chest pain. The management of these disorders remain a challenge for the clinician. Pharmacotherapy, botulinum toxin injection, endoscopic dilation, and laparoscopic Heller myotomy have been employed, with limited efficacy in the majority of patients. Currently, there are no controlled studies in literature that suggest which is the best management of these diseases. Since its introduction in clinical practice, PerOral Endoscopic Myotomy (POEM) has emerged as a very promising, minimally invasive and effective treatment for oesophageal achalasia. No longer after the first uses, POEM has been successfully used also for the management of selected patients with NAOMD, However, currently available data are limited by small study sample sizes and short-term follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: There exists a paucity of data regarding the mechanism and manometric findings in retrograde cricopharyngeal dysfunction (RCPD). In this study, we aimed to compare esophageal physiologic findings between patients with RCPD compared to an asymptomatic cohort., Study Design: Case-control study., Setting: Tertiary Care Center., Methods: Esophageal high-resolution impedance manometry was completed preoperatively in patients diagnosed with RCPD. Manometric data were compared between the RCPD and asymptomatic cohorts. A 2:1 age-sex-matched asymptomatic cohort was used as the control group. Treatment response was assessed among the RCPD cohort., Results: Thirty-nine patients are included: 13 RCPD [mean age: 31.1 (SD: 12.6) years, female sex: 11 (85%)] and 26 asymptomatic [mean age: 32.1 (SD: 1.5) years, female sex: 22 (85%)]. The RCPD cohort, compared to the asymptomatic cohort, exhibited significantly greater upper esophageal sphincter (UES) length [4.5 (SD: 0.7) vs 3.7 (0.9) cm, P = .01] and higher UES basal pressures [91.9 (35.0) vs 49.7 (25.5) mm Hg, P = .002]. Patients with RCPD demonstrated higher rates of ineffective swallows [70.0% (31.6%) vs 15.4% (21.6%), P < .001] and incomplete bolus clearance [81% (22.0%) vs 21.8% (30.0%), P < .001]. All patients who underwent cricopharyngeal botulinum injections experienced initial improvement of symptoms with 3 patients requiring repeat intervention., Conclusion: RCPD is associated with a longer UES, elevated UES basal pressures, and an increased incidence of ineffective esophageal motility. This study is the first to compare preoperative manometry results among patients with RCPD to those of an asymptomatic cohort, providing insights into the mechanism of RCPD., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Esophageal motility disorders can be diagnosed by either high-resolution manometry (HRM) or the functional lumen imaging probe (FLIP) but there is no systematic approach to synergize the measurements of these modalities or to improve the diagnostic metrics that have been developed to analyze them. This work aimed to devise a formal approach to bridge the gap between diagnoses inferred from HRM and FLIP measurements using deep learning and mechanics., Methods: The "mechanical health" of the esophagus was analyzed in 740 subjects including a spectrum of motility disorder patients and normal subjects. The mechanical health was quantified through a set of parameters including wall stiffness, active relaxation, and contraction pattern. These parameters were used by a variational autoencoder to generate a parameter space called virtual disease landscape (VDL). Finally, probabilities were assigned to each point (subject) on the VDL through linear discriminant analysis (LDA), which in turn was used to compare with FLIP and HRM diagnoses., Results: Subjects clustered into different regions of the VDL with their location relative to each other (and normal) defined by the type and severity of dysfunction. The two major categories that separated best on the VDL were subjects with normal esophagogastric junction (EGJ) opening and those with EGJ obstruction. Both HRM and FLIP diagnoses correlated well within these two groups., Conclusion: Mechanics-based parameters effectively estimated esophageal health using FLIP measurements to position subjects in a 3-D VDL that segregated subjects in good alignment with motility diagnoses gleaned from HRM and FLIP studies., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, and more than 80% of PD patients will develop oropharyngeal dysphagia. Despite its striated histology, proximity to airway, and potential negative impact of its dysfunction on bolus transport and airway safety, the contractile function of the striated esophagus in PD patients has not been systematically studied., Methods: Using our repository of clinical manometry and the Milwaukee ManoBank, we analyzed high-resolution manometry (HRM) studies of 20 PD patients, mean age 69.1 (range 38-87 years); 30 non-PD patients with dysphagia, mean age 64.0 (44-86 years); and 32 healthy volunteers, mean age 65.3 (39-86 years). Patients with abnormal findings based on Chicago Classification 4.0 were identified. Repeat analysis was performed in 20% of the manometric tracings by a different investigator with inter-rater concordance between 0.91 and 0.99., Key Results: The striated esophageal contractile integral in PD patients was significantly lower than that in non-PD dysphagic patients and healthy controls (p = 0.03 and <0.01, respectively). This significant difference persisted after excluding patients with concurrent Chicago Classification motility disorders (p = 0.02 and 0.01, respectively). In both analyses, the distal esophageal contractile integral did not show any significant difference between groups (p = 0.58 and 0.93, respectively)., Conclusions & Inferences: PD is associated with a significant decrease in striated esophagus contractility compared to non-PD and healthy controls. This finding may play a pathophysiologic role in development of dysphagia in this patient population., (© 2024 John Wiley & Sons Ltd.)

Background: Diabetes Mellitus (DM) is known to induce a wide range of harmful effects on several organs, notably leading to ineffective esophageal motility (IEM). However, the relationship between DM and IEM is not fully elucidated. We aimed to determine the relationship between DM and IEM and to evaluate the impact of DM's end organ complications on IEM severity., Methods: A multicenter cohort study of consecutive patients undergoing high-resolution esophageal manometry (HREM) was performed. We reviewed medical records of patients diagnosed with IEM using HREM, encompassing data on demographics, DM history, antidiabetic and other medications as well as comorbidities., Key Results: Two hundred and forty six subjects met the inclusion criteria. There was no significant difference in any of the HREM parameters between diabetics and nondiabetics. Out of 246 patients, 92 were diabetics. Diabetics with neuropathy presented a significantly lower distal contractile integral (DCI) value compared to those without neuropathy (248.2 ± 226.7 mmHg·cm·sec vs. 375.6 ± 232.4 mmHg·cm·sec; p = 0.02) Similarly, the DCI was lower in diabetics with retinopathy compared to those without retinopathy (199.9 ± 123.1 mmHg·cm·sec vs. 335.4 ± 251.7 mmHg·cm·sec; p = 0.041). Additionally, a significant difference was observed in DCI values among DM patients with ≥2 comorbidities compared to those without comorbidities (224.8 ± 161.0 mmHg·cm·sec vs. 394.2 ± 243.6 mmHg·cm·sec; p = 0.025). Around 12.6% of the variation in DCI could be explained by its linear relationship with hemoglobin A1c (HbA1c), with a regression coefficient (β) of -55.3., Conclusion & Inferences: DM is significantly associated with IEM in patients with neuropathy, retinopathy, or multiple comorbidities. These results are pivotal for tailoring patient-specific management approaches., (© 2024 John Wiley & Sons Ltd.)

The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)-free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan-Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The current definition for hypercontractile esophagus was arbitrarily set at the uppermost range in volunteers for a specific equipment., Objective: This study aims to critically analyze the concept of hypercontractile waves to redefine hypercontractile esophagus parameters., Methods: We reviewed 500 unselected and consecutive HRM tests (5000 waves) performed in a water -perfused system., Results: Mean distal contractility integral (DCI) was 825±1492 (0-42775) mmHg.cm.s, two standard deviations above average = 3810; 95th percentile = 2798 mmHg.cm.s., Conclusion: In healthy volunteers, two standard deviations above average is 4000 mmHg.cm.s, we thus suggest this value to define hypercontractile waves and define hypercontractile esophagus in a water-perfused HRM system.

Purpose of Review: To review recent publications on the inability to belch syndrome., Recent Findings: Five recent retrospective case series indicate that the inability to belch syndrome usually starts in early childhood and is often accompanied by gurgling noises in the chest, pain in the chest or upper abdomen, bloating, and excessive flatulence. Currently, the vast majority of patients who have been identified with inability to belch have self-diagnosed the syndrome on the basis of information available on the internet. A favorable response to injection of botulinum toxin in the cricopharyngeus muscle is regarded as confirmation of the diagnosis. In a mechanistic study in eight patients, absence of reflexogenic relaxation of the upper esophageal sphincter upon rapid gaseous esophageal distension was confirmed to play a pivotal role in the pathogenesis of the syndrome., Summary: The inability to belch syndrome, caused by failure of the upper esophageal sphincter to relax when the esophageal body is distended, clearly exists and may not be as rare as thought hitherto. However, overdiagnosis is also likely to occur because the diagnosis is usually made on the basis of symptoms only. The efficacy of botulinum toxin injection in the upper sphincter needs to be assessed in double-blind placebo-controlled studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The objective measurement for esophageal bolus volume and bolus clearance could classify abnormal high-resolution manometry (HRM) beyond the current Chicago classification. We aimed to compare the novel four-dimensional impedance manometry (4D HRM) volume metrics with timed barium esophagram (TBE)., Methods: Adults with esophageal symptoms undergoing HRM and TBE were included. A custom-built program for 4D HRM analysis measured esophageal luminal cross-sectional area (CSA) from impedance and subsequently derived esophageal bolus volume and clearance. 4D HRM volume metrics included pre-swallow residual volume, maximal volume, retention volume, and clearance ratio defined as 1.0-retention volume divided by the maximal volume. An abnormal TBE was defined as a column height >5 cm at 1 min or 5 min., Key Results: A total of 95 patients (normal motility: 33%; ineffective esophageal motility: 12%; absent contractility: 10%; esophagogastric junction outflow obstruction: 30%; type I achalasia: 5%; type II achalasia: 12%) were categorized into normal TBE (58%), abnormal TBE at 1 min (17%), and abnormal TBE at 5 min (25%). The AUROC demonstrated that, among all 4D HRM volume metrics, the clearance ratio had the best performance in predicting abnormal TBE at 5 min (AUROC, 95% confidence interval: 0.89, 0.82-0.96), and exhibited a strong negative correlation with TBE at 5 min (r = -0.65; p < 0.001)., Conclusions & Inferences: Novel 4D HRM volume metrics provide objective measurement of esophageal bolus volume and bolus clearance. The clearance ratio has a strong correlation with TBE and could potentially serve as a substitute for TBE to measure esophageal retention., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Purpose of Review: Esophagogastric junction outflow obstruction (EGJOO), defined manometrically by impaired esophagogastric junction relaxation (EGJ) with preserved peristalsis, can be artifactual, due to secondary etiologies (mechanical, medication-induced), or a true motility disorder. The purpose of this review is to go over the evolving approach to diagnosing and treating clinically relevant EGJOO., Recent Findings: Timed barium esophagram (TBE) and the functional lumen imaging probe (FLIP) are useful to identify clinically relevant EGJOO that merits lower esophageal sphincter (LES) directed therapies. There are no randomized controlled trials evaluating EJGOO treatment. Uncontrolled trials show effectiveness for pneumatic dilation and peroral endoscopic myotomy to treat confirmed EGJOO; Botox and Heller myotomy may also be considered but data for confirmed EGJOO is more limited. Diagnosis of clinically relevant idiopathic EGJOO requires symptoms, exclusion of mechanical and medication-related etiologies, and confirmation of EGJ obstruction by TBE or FLIP. Botox LES injection has limited durability, it can be used in patients who are not candidates for other treatments. PD and POEM are effective in confirmed EGJOO, Heller myotomy may also be considered but data for confirmed EGJOO is limited. Randomized controlled trials are needed to clarify optimal management of EGJOO., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Functional lumen imaging probe (FLIP) panometry evaluates esophageal motility, including the contractile response to distension, that is, secondary peristalsis. Impaired/disordered contractile response (IDCR) is an abnormal, but nonspecific contractile response that can represent either hypomotility or spastic motor disorders on high-resolution manometry (HRM). We hypothesized that FLIP pressure could be incorporated to clarify IDCR and aimed to determine its utility in a cohort of symptomatic esophageal motility patients., Methods: 173 adult patients that had IDCR on FLIP panometry and HRM with a conclusive Chicago Classification v4.0 (CCv4.0) diagnosis were included and analyzed as development (n = 118) and validation (n = 55) cohorts. FLIP pressure values were assessed for prediction of either hypomotility or spasm, defined on HRM/CCv4.0., Key Results: HRM/CCv4.0 diagnoses were normal motility in 48 patients (28%), "hypomotility" (ineffective esophageal motility, absent contractility, or Type I or II achalasia) in 89 (51%), and "spasm" (Type III achalasia, distal esophageal spasm, or hypercontractile esophagus) in 36 (21%). The pressure at esophagogastric junction-distensibility index (DI) (60 mL) was lower in hypomotility (median [interquartile range] 34 [28-42] mmHg) than in spasm (49 [40-62] mmHg; p < 0.001) and had an area under the receiver operating characteristic curve of 0.80 (95% CI 0.73-0.88) for hypomotility and 0.76 (0.69-0.83) for spasm. For "spasm" on HRM, a threshold FLIP pressure of >35 mmHg provided 90% sensitivity (47% specificity) while >55 mmHg provided 93% specificity (40% sensitivity)., Conclusion & Inferences: Pressure on FLIP panometry can help clarify the significance of IDCR, with low-pressure IDCR associated with hypomotility and high-pressure IDCR suggestive of spastic motor disorders., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background: Chagas disease causes digestive anatomic and functional changes, including the loss of the myenteric plexus and abnormal esophageal radiologic and manometric findings., Objective: To evaluate the association of abnormal esophageal radiologic findings, cardiac changes, distal esophageal contractions, and complaints of dysphagia and constipation in upper (UES) and lower (LES) esophageal sphincter basal pressure in Chagas disease patients., Methods: The study evaluated 99 patients with Chagas disease and 40 asymptomatic normal volunteers. The patients had normal esophageal radiologic examination (n=61) or esophageal retention without an increase in esophageal diameter (n=38). UES and LES pressure was measured with the rapid pull-through method in a 4-channel water-perfused round catheter. Before manometry, the patients were asked about dysphagia and constipation and submitted to electrocardiography and chest radiography., Results: The amplitude of esophageal distal contraction decreased from controls to chagasic patients with esophageal retention. The proportion of failed and simultaneous contractions increased in patients with abnormal radiologic examination (P<0.01). There were no significant differences in UES and LES pressure between the groups. UES pressure was similar between Chagas disease patients with cardiomegaly (n=27, 126.5±62.7 mmHg) and those without it (n=72, 144.2±51.6 mmHg, P=0.26). Patients with constipation had lower LES pressure (n=23, 34.7±20.3 mmHg) than those without it (n=76, 42.9±20.5 mmHg, P<0.03)., Conclusion: Chagas disease patients with absent or mild esophageal radiologic involvement had no significant changes in UES and LES basal pressure. Constipation complaints are associated with decreased LES basal pressure.

Background: For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed., Methods: We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33-75 years; 42 men) who underwent high resolution impedance manometry and 24-h pH-impedance before and after LTx., Key Results: RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post-LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre-LTx (p < 0.001), reducing only in OLD patients' post-LTx (p = 0.02). Reduced EL post-LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco-abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05)., Conclusions and Inferences: RLD patients are more likely to show improvement in esophageal motility than OLD patients post-LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Motility disorders are frequently encountered in gastroenterology (GI) practice, yet a national structured training curriculum for GI fellows in motility disorders is lacking. Since GI fellowships vary considerably in opportunities for specialized esophageal motility (EM) training, novel educational technology may be leveraged to provide standardized EM curriculum to train GI fellows in esophageal manometry., Methods: GI fellows participated in an online EM learning program at a single academic center from 2017 to 2022. Fellows answered case-based questions and were provided with evidence-based, corrective feedback related to core EM learning objectives. The primary outcome was change in knowledge and comfort in interpretation and clinical application of EM studies., Results: Sixty-nine fellows actively participated in the online EM curriculum. 65 fellows completed a pre-curriculum test, and 54 fellows completed a post-curriculum test. There was a cumulative improvement between pre-curriculum test and post-curriculum test scores from 70 to 87%, respectively (p < 0.001). Fellows had a mean improvement of 19% in questions as they progressed through the curriculum. Prior to enrolling in the EM course, 26% of fellows felt comfortable in interpreting EM studies compared to 54% of fellows after completion of the program (p < 0.001)., Conclusion: An online, technology-based curriculum was effective in educating GI fellows on core competencies of EM. Fellows demonstrated improvement in proficiency of clinically important EM studies and increased comfort in interpreting EM studies. Further studies are needed to evaluate the use of technology-based learning to widely disseminate a structured training curriculum in EM, particularly in training programs without a motility presence., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The inability to burp, known as retrograde cricopharyngeal dysfunction (R-CPD), was initially described in adults. The proposed clinical diagnostic criteria for R-CPD include belching inability, abdominal bloating and discomfort/nausea, postprandial chest pain, and involuntary noises. Botulinum toxin injection to the cricopharyngeal muscle has been reported to be beneficial. High-resolution esophageal impedance-manometry (HRIM) features in adolescent patients with R-CPD have not been described yet.  The aim of our study was to describe the clinical and HRIM findings of pediatric patients with R-CPD., Methods: Clinical and manometric features of five pediatric patients diagnosed with R-CPD were reviewed. HRIM study protocol was modified to include the consumption of carbonated drink to provoke symptoms and distinctive manometric features., Results: We report five female patients aged 15-20 years who presented with an inability to burp and involuntary throat sounds. HRIM revealed normal upper esophageal sphincter (UES) relaxation during swallowing, but abnormal UES relaxation with concurrent high esophageal impedance reflecting air entrapment and secondary peristalsis following the carbonated drink challenge. Four patients exhibited esophageal motility disorder. All patients reported improvement or resolution of symptoms after botulinum toxin injection to the cricopharyngeus muscle., Conclusions: Adolescents with an inability to burp, reflux-like symptoms, bloating, and involuntary throat noises should be assessed for R-CPD by pediatric gastroenterologists with HRIM. The relatively recent recognition of this novel condition is the likely reason for its under- and misdiagnosis in children., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: The EndoFLIP (for its acronym in English: endoluminal functional luminal probe) is a system that measures in real time the compliance index of the gastroesophageal junction and secondary esophageal peristalsis, based on the principle of impedance planimetry. Although this technology is relatively new and its diagnostic usefulness is still being evaluated, its use in clinical practice is increasingly recognized, fundamentally in those patients where there is no conclusive manometric diagnosis of esophageal motor pathology, mainly esophagogastric junction outflow obstruction and achalasia., Objective: The aim of the present study is to describe the experience with EndoFLIP at the San Ignacio University Hospital in Bogotá, Colombia., Material and Methods: Descriptive observational case series study, which included patients over 18 years of age who had undergone EndoFLIP at the San Ignacio University Hospital from 2021 to 2022, either in-hospital or outpatient, with a clear indication of performance of the study, previously discussed in the multidisciplinary Gastroenterology Board., Results: A total of 27 patients with an average age of 55 years were included in the study, of which 20 were women (74%) and 7 men (26%). The most frequent indication of the study was an inconclusive diagnosis of outflow tract obstruction identified in high-resolution esophageal manometry according to Chicago 4.0 criteria (14 patients), followed by hypercontractile esophagus (4 patients) and ineffective esophageal motility (3 patients). When evaluating the contractile response, it was found that 9 patients with an inconclusive diagnosis of outflow tract obstruction had a normal response, 3 absent and one altered; and in the patients with an inconclusive diagnosis of achalasia, one of them had a borderline contractile response and two had no response. All patients with a previous diagnosis of absent contractility had an equally absent contractile response in EndoFLIP., Conclusion: Endoluminal functional luminal imaging is a technique that evaluates biomechanical properties such as distensibility, volume, pressure and even diameters of sphincter regions such as the gastroesophageal junction, pylorus and anus. Its usefulness has been highlighted for several indications, the most important being manometrically inconclusive diagnoses of esophageal motor disorders such as achalasia and outflow tract obstruction, pathologies that have a significant impact on the quality of life of patients and whose diagnosis is essential to be able to provide the best treatment option.

Background: Reason for dysphagia in a significant number of patients remains unclear even after a thorough workup. Each swallow induces esophageal distension followed by contraction of the esophagus, both of which move sequentially along the esophagus. Manometry technique and current system of classifying esophageal motility disorders (Chicago Classification) is based on the analysis of the contraction phase of peristalsis., Goal: Whether patients with unexplained dysphagia have abnormalities in the distension phase of esophageal peristalsis is not known., Methods: Using Multiple Intraluminal esophageal impedance recordings, which allow determination of the luminal cross-sectional area during peristalsis, we studied patients with nutcracker esophagus (NC), esophagogastric junction outflow obstruction (EGJOO), and functional dysphagia (FD)., Results: Distension contraction plots revealed that swallowed bolus travels significantly faster through the esophagus in all patient groups as compared to normals. The luminal cross-sectional area (amplitude of distension), and the area under the curve of distension were significantly smaller in patients with NC, EGJOO, and FD as compared to normals. Bolus traverses the esophagus in the shape of an "American Football" in normal subjects. On the other hand, in patients the bolus flow was fragmented. ROC curves revealed that bolus flow abnormalities during peristalsis are a sensitive and specific marker of dysphagia., Conclusion: Our findings reveal abnormality in the distension phase of peristalsis (a narrow lumen esophagus) in patients with dysphagia. We propose that the esophageal contraction forcing the swallowed bolus through a narrow lumen esophagus is the cause of dysphagia sensation in patients with normal contraction phase of peristalsis., Competing Interests: Dr Zifan and Dr Mittal have copyright protection for the computer software (Dplots). However, this does not alter in any way our adherence to PLOS ONE policies on sharing data and materials.

Background and Aims: This study aimed to systematically evaluate a classification scheme of secondary peristalsis using functional luminal imaging probe (FLIP) panometry through comparison with primary peristalsis on high-resolution manometry (HRM)., Methods: 706 adult patients that completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers ("controls") were included. Secondary peristalsis, that is, contractile responses (CRs), was classified on FLIP panometry by the presence and pattern of contractility as normal (NCR), borderline (BCR), impaired/disordered (IDCR), absent (ACR), or spastic-reactive (SRCR). Primary peristalsis on HRM was assessed according to the Chicago Classification., Results: All 35 of the controls had antegrade contractions on FLIP panometry with either NCR (89%) or BCR (11%). The average percentages of normal swallows on HRM varied across contractile response patterns from 84% in NCR, 68% in BCR, 39% in IDCR, to 11% in ACR, as did the percentage of failed swallows on HRM: 4% in NCR, 12% in BCR, 36% in IDCR, and 79% in ACR. SRCR on FLIP panometry was observed in 18/57 (32%) patients with type III achalasia, 4/15 (27%) with distal esophageal spasm, and 7/15 (47%) with hypercontractile esophagus on HRM., Conclusions: The FLIP panometry contractile response patterns reflect a pathophysiologic transition from normal to abnormal esophageal peristaltic function with shared features with primary peristaltic function/dysfunction on HRM. Thus, these patterns of the contractile response to distension can facilitate the evaluation of esophageal motility using FLIP panometry., (© 2021 John Wiley & Sons Ltd.)

Introduction: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0)., Methods: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., secondary peristalsis) were evaluated with a 16-cm FLIP during sedated endoscopy and analyzed using a customized software program. HRM was classified according to CCv4.0., Results: In the primary analysis, 156 patients (29%) had normal motility on FLIP panometry, defined by normal EGJ opening and a normal or borderline CR; 95% of these patients had normal motility or ineffective esophageal motility on HRM. Two hundred two patients (37%) had obstruction with weak CR, defined as reduced EGJ opening and absent CR or impaired/disordered CR, on FLIP panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0., Discussion: Classifying esophageal motility in response to sustained distension with FLIP panometry parallels the swallow-associated motility evaluation provided with HRM and CCv4.0. Thus, FLIP panometry serves as a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: High amplitude peristaltic esophageal contractions, that is, nutcracker esophagus, were originally described in association with "angina-like pain" of esophageal origin. However, significant number of nutcracker patients also suffer from dysphagia. High-resolution esophageal manometry (HRM) assesses only the contraction phase of peristalsis. The degree of esophageal distension during peristalsis is a surrogate of relaxation and can be measured from the intraluminal esophageal impedance measurements., Aims: Determine the amplitude of distension and temporal relationship between distension and contraction during swallow-induced peristalsis in nutcracker patients., Methods: HRM impedance (HRMZ) studies were performed and analyzed in 24 nutcracker and 30 normal subjects in the Trendelenburg position. A custom-built software calculated the numerical data of the amplitudes of distension and contraction, the area under the curve (AUC) of distension and contraction, and the temporal relationship between distension and contraction., Results: In normal subjects, the distension peaks similar to contraction traverse sequentially the esophagus. The amplitude of contraction is greater in the nutcracker esophagus but the amplitude of distension and area under the curve of distension are smaller in patients compared to controls. Distension peaks are aligned closely with contraction in normal subjects, but in patients, the bolus travels faster to the distal esophagus, resulting in a smaller time interval between the onset of swallow and distension peak. Receiver operative characteristics (ROC) curve reveals high sensitivity and specificity of the above parameters in patients., Conclusion: Abnormalities in the distension phase of peristalsis are a possible mechanism of dysphagia in patients with nutcracker esophagus., (© 2021 John Wiley & Sons Ltd.)

Esophageal hypomotility disorders manifest with abnormal esophageal body contraction vigor, breaks in peristaltic integrity, or failure of peristalsis in the context of normal lower esophageal sphincter relaxation on esophageal high-resolution manometry (HRM). The Chicago Classification version 4.0 recognizes two hypomotility disorders, ineffective esophageal motility (IEM) and absent contractility, while fragmented peristalsis has been incorporated into the IEM definition. Updated criteria for ineffective swallows consist of weak esophageal body contraction vigor measured using distal contractile integral (DCI, 100-450 mmHg·cm·s), transition zone defects >5 cm measured using a 20 mmHg isobaric contour, or failure of peristalsis (DCI < 100 mmHg·cm·s). More than 70% ineffective swallows and/or ≥50% failed swallows are required for a conclusive diagnosis of IEM. When the diagnosis is inconclusive (50%-70% ineffective swallows), supplementary evidence from multiple rapid swallows (absence of contraction reserve), barium radiography (abnormal bolus clearance), or HRM with impedance (abnormal bolus clearance) could support a diagnosis of IEM. Absent contractility requires 100% failed peristalsis, consistent with previous versions of the classification. Consideration needs to be given for the possibility of achalasia in absent contractility with dysphagia despite normal IRP, and alternate complementary tests (including timed upright barium esophagram and functional lumen imaging probe) are recommended to confirm or refute the presence of achalasia. Future research to quantify esophageal bolus retention on stationary HRM with impedance and to understand contraction vigor thresholds that predict bolus clearance will provide further refinement to diagnostic criteria for esophageal hypomotility disorders in future iterations of the Chicago Classification., (© 2021 John Wiley & Sons Ltd.)

Introduction : Esophagus dysmotility is a crucial risk factor of gastroesophageal reflux disease (GERD), which is one of the most common diseases in digestive medicine globally. This review emphasizes the mechanisms of esophagus dysmotility in diabetes and summarizes more targeted treatments for these patients to avoid the overuse of proton pump inhibitors (PPIs). Areas covered : Diabetes mellitus (DM) is a clear factor that must not be neglected in the development of GERD. Previous studies have preliminarily researched the esophagus deterioration in diabetes. However, the multi-faceted mechanisms of esophagus dysmotility in diabetes need more studies. Besides, targeted treatments for these patients rather than conventional PPIs are urgently needed. Expert opinion : The treatments for GERD patients with diabetes should be further explored. Pharmacological approaches such as prokinetic agents, psychotherapy can be adopted. Meanwhile, it's feasible to explore non-drug treatments. For example, Electroacupuncture (EA) at Zusanli (ST-36) may be effective to protect the networks of intestinal cells of Cajal (ICCs) in diabetes. More effective approaches should be explored to achieve individualized treatment for these patients.

Background: Esophageal hypercontractility (EHC) is considered a major esophageal motor disorder of unclear etiology. Different mechanisms have been proposed, including an imbalance in inhibitory and excitatory esophageal innervation. We hypothesized that patients with EHC suffer from cholinergic hyperactivity., Aim: To interrogate the excitatory and inhibitory neurotransmission in EHC by assessing the esophageal motor response to atropine (ATR) and cholecystokinin (CCK), respectively, in EHC patients., Method: We retrospectively reviewed patients who underwent high-resolution manometry (HRM) with pharmacologic challenge in a tertiary referral center between 2007 and 2017. We identified 49 EHC patients who were categorized based on frequency of hypercontractile peristaltic sequence into "frequent" and "infrequent" and motility diagnosis groups. Deglutitive pressure metrics and esophageal motor responses to ATR (12 mcg/kg iv) and CCK (40 ng/kg iv) were analyzed across groups., Results: Atropine abolished hypercontractility across all groups studied, converting nearly half of patients to a motor pattern of ineffective esophageal motility. Abnormal CCK responses primarily occurred in the patient groups with concomitant outflow obstruction., Conclusions: Hypercontractility is cholinergically mediated in all esophageal motor disorders. Most patients with isolated EHC appear to have excessive cholinergic drive, rather than loss of inhibitory innervation, and might be candidates for treatment with anticholinergic agents., (© 2020 John Wiley & Sons Ltd.)

Introduction: Impaired esophageal and gastric motilities are known to contribute to symptoms of gastroesophageal reflux disease (GERD). However, there is a lack of GERD therapy, targeting both gastric and esophageal functions. This study was designed to investigate the effects of transcutaneous electrical acustimulation (TEA) on symptoms of GERD and gastroesophageal functions and possible mechanisms in patients with GERD., Methods: Thirty patients with GERD with ineffective esophageal motility were equally divided and randomized into a 4-week sham-TEA or 4-week TEA treatment. The GERD questionnaire (GerdQ), GERD health-related quality-of-life questionnaire, high-resolution esophageal manometry, a nutrient drink test, the electrogastrogram, and ECG were performed to assess the severity of reflux symptoms, low esophageal sphincter (LES) pressure, distal contractile integral (DCI), gastric accommodation, gastric slow waves (GSW), and autonomic functions, respectively., Results: Compared with sham-TEA, the 4-week TEA treatment significantly decreased the GerdQ score (P = 0.011) and GERD health-related quality of life (P = 0.028) and improved nutrient drink-induced fullness (P < 0.001) and belching (P < 0.001) in patients with GERD. Although only acute TEA significantly enhanced LES pressure (P < 0.05), both acute and chronic TEA remarkedly increased DCI (P < 0.05) and reduced the incidence of ineffective esophageal contractions during wet swallows (P = 0.02). In addition, chronic TEA significantly increased gastric accommodation and the percentage of postprandial normal GSW compared with sham-TEA and baseline. Concurrently, TEA-enhanced vagal activity (P = 0.02) and the vagal activity positively correlated with LES pressure (r = 0.528; P = 0.003) and DCI (r = 0.522; P = 0.003)., Discussion: The TEA treatment performed in this study improves reflux-related symptoms, increases DCI, reduces the incidence of ineffective esophageal contractions during wet swallows, and improves gastric accommodation and slow waves. The improvement in GERD symptoms might be attributed to the integrative effects of TEA on these gastroesophageal functions mediated via the vagal mechanism., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF., Methods: We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment., Results: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008)., Discussion: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs., (Copyright © 2021 by The American College of Gastroenterology.)

Background: Several patients in gastroenterology practice present with esophageal symptoms, and in case of normal endoscopy with biopsies, high-resolution manometry (HRM) is often the next step. Our aim was to develop a European consensus on the clinical application of esophageal HRM, to offer the clinician guidance in selecting patients for HRM and using its results to optimize clinical outcome., Methods: A Delphi consensus was initiated with 38 multidisciplinary experts from 16 European countries who conducted a literature summary and voting process on 71 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 statements., Results: The process generated guidance on when to consider esophageal HRM, how to perform it, and how to generate the report. The Delphi process also identified several areas of uncertainty, such as the choice of catheters, the duration of fasting and the position in which HRM is performed, but recommended to perform at least 10 5-ml swallows in supine position for each study. Postprandial combined HRM impedance is considered useful for diagnosing rumination. There is a large lack of consensus on treatment implications of HRM findings, which is probably the single area requiring future targeted research., Conclusions and Inferences: A multinational and multidisciplinary group of European experts summarized the current state of consensus on technical aspects, indications, performance, analysis, diagnosis, and therapeutic implications of esophageal HRM., (© 2020 John Wiley & Sons Ltd.)

Introduction: Patients with esophageal symptoms often remain with an uncertain diagnosis after high-resolution manometry., Aim: To determine the added value of concomitant pressure and symptom analysis in response to a rapid drink challenge (RDC)., Methods: In consecutive patients referred for esophageal manometry, a RDC consisting in free drinking of 200 ml of water as quick as possible was performed after the standard single water swallows manometry. Both pressure patterns and usual symptoms induced by the RDC were analyzed., Results: A total of 1319 patients were included, (64.7% women, mean age 58.2 years, range 11-90). There were significant differences in pressure responses between patients with obstructive disorders, major hypercontractile disorders, esophageal hypomotility disorders and normal motility. The RDC provoked usual symptoms in 388 (29.4%) patients, associated with hyperpressive and obstructive patterns in 14.0% and 16.6%, respectively. Reproduction of dysphagia and regurgitation (not pain) was significantly associated with abnormal pressure responses during the RDC (p < 0.001 and p = 0.002, respectively). The RDC elicited both abnormal pressure patterns and symptoms in 6.2%, 1.6%, and 20.8% of patients with normal motility, ineffective esophageal motility, and esophago-gastric junction outflow obstruction, respectively., Conclusion: Concomitant evaluation of symptoms and pressure responses to a RDC may increase the specificity of esophageal motor testing in patients with inconclusive diagnosis or normal esophageal motility., (© 2020 John Wiley & Sons Ltd.)

The Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). A key feature of CCv.4.0 is the more rigorous and expansive protocol that incorporates single wet swallows acquired in different positions (supine, upright) and provocative testing, including multiple rapid swallows and rapid drink challenge. Additionally, solid bolus swallows, solid test meal, and/or pharmacologic provocation can be used to identify clinically relevant motility disorders and other conditions (eg, rumination) that occur during and after meals. The acquisition and analysis for performing these tests and the evidence supporting their inclusion in the Chicago Classification protocol is detailed in this technical review. Provocative tests are designed to increase the diagnostic sensitivity and specificity of HRM studies for disorders of esophageal motility. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification, decrease the proportion of HRM studies that deliver inconclusive diagnoses and increase the number of patients with a clinically relevant diagnosis that can direct effective therapy. Another aim in establishing a standard manometry protocol for motility laboratories around the world is to facilitate procedural consistency, improve diagnostic reliability, and promote collaborative research., (© 2021 John Wiley & Sons Ltd.)

Background/aim: The aim was to investigate whether there is a difference in secondary peristalsis on high-resolution manometry (HRM) among gastroesophageal reflux disease (GERD) patients with and without ineffective esophageal motility (IEM), and healthy individuals., Methods: Twenty-eight GERD patients and seventeen healthy controls were included. Secondary peristalsis was stimulated by a rapid injection of 20 ml air in mid-esophagus. We compared HRM metrics and the response and effective rate of triggering secondary peristalsis between patients with and without IEM and healthy controls., Results: Sixteen patients had IEM, and the remaining 12 had normal manometry. By triggering of secondary peristalsis, patients without IEM and healthy controls had significantly higher distal contractile integral (DCI) values than IEM patients (p = 0.006). A successful secondary peristalsis was triggered more frequently in healthy controls than in GERD patients with normal peristalsis or IEM (56.9% vs. 20.2% vs. 9.1%, all p < 0.001). The effective rate which determined as DCI > 450 mm Hg.cm.s was higher in healthy controls compared to patients with normal peristalsis (36.5% vs. 19.4%, p < 0.001) and IEM (36.5% vs. 6.3%, p < 0.001). Patients with IEM had lower successful triggering response (9.1% vs. 20.2%) and effective secondary peristalsis (6.3% vs. 19.4%) compared with patients without IEM (p < 0.001)., Conclusions: Our work has demonstrated that GERD patients, in particular those with IEM, have significant defects in the triggering of secondary peristalsis on HRM. HRM helps characterize esophageal secondary peristalsis which exhibits differently in patients with and without IEM., (© 2020 John Wiley & Sons Ltd.)

Objectives: Esophageal dysmotility (ED) in patients with multiple system atrophy (MSA) are poorly understood. This study aimed to investigate the prevalence of ED in patients with MSA and to assess the relationship of esophageal abnormalities with other clinical findings and characteristics in these patients., Methods: A retrospective chart review was conducted to identify patients with MSA and to compare them to the elderly controls without MSA (65+ years) who underwent a videofluorographic esophagram from 2014 to 2019. Disease type, disease severity, vocal fold mobility impairment, abnormal deglutitive proximal esophageal contraction (ADPEC), and intra-esophageal stasis (IES) were reviewed and compared between groups., Results: Thirty-seven patients with MSA were identified. The median age was 63 and 26 (70%) were male. These patients were matched to 22 elderly adults with presbylarynx but not MSA (median age 77, 68% male). In MSA patients, cerebellar variant type was predominant (59%), and ADPEC was recognized in 18 patients (49%). Disease severity level (P = 0.028) and existence of IES (P = 0.046) were associated with higher risks of developing ADPEC. The prevalence of IES was significantly higher in patients with MSA (95%) compared to controls without MSA (46%) (P < 0.001). Disease severity level and the existence of IES were significantly associated with the presence of ADPEC (p < 0.05)., Conclusion: ADPEC and IES were significantly more common in MSA than in elderly subjects without MSA. MSA severity is associated with the development of ADPEC. The data suggest that esophageal motility is predominantly affected in MSA., Level of Evidence: 3 Laryngoscope, 131:832-838, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Esophagogastric junction outflow obstruction (EGJOO) as defined by Chicago Classification of esophageal motility disorders (CCv3.0) encompasses a broad range of diagnoses, thus posing clinical challenges. Our aims were to evaluate multiple rapid swallow (MRS) and rapid drink challenge (RDC) during high-resolution manometry (HRM) to aid identifying clinically relevant EGJOO., Methods: Patients with a HRM diagnosis of EGJOO based on CCv3.0 that also completed MRS and RDC during HRM and barium esophagram were retrospectively identified. Radiographic EGJOO (RAD-EGJOO) was defined by either liquid barium retention or delayed passage of a barium tablet on barium esophagram. Thirty healthy asymptomatic controls that completed HRM were also included. MRS involved drinking 2 mL for 5 successive swallows. RDC involved rapid drinking of 200 mL liquid. Integrated relaxation pressure (IRP) and presence of panesophageal pressurization (PEP) during MRS and RDC were assessed., Key Results: One hundred one patients, mean (SD) age 56 (16) years, were included; 32% had RAD-EGJOO, 68% did not. RAD-EGJOO patients more frequently had elevated (>12 mmHg) upright IRP (100%), MRS-IRP (56%), RDC-IRP (53%), and PEP during RDC (66%) than both controls [17%; 0%; 7%; 3%] and patients without RAD-EGJOO [83%; 35%; 39%; 41%] Having IRP >12 mmHg during both MRS and RDC was twice as likely to be associated with RAD-EGJOO (19%) than those without RAD-EGJOO (9%) among patients with upright IRP >12 mmHg., Conclusions and Inferences: Adjunctive HRM maneuvers MRS and RDC appear to help identify clinically significant EGJOO. While future outcome studies are needed, comprehensive multimodal evaluation helps clarify relevance of EGJOO on HRM., (© 2020 John Wiley & Sons Ltd.)

Hypercontractile esophagus (HE) is a heterogeneous major motility disorder diagnosed when ≥20% hypercontractile peristaltic sequences (distal contractile integral >8,000 mm Hg*s*cm) are present within the context of normal lower esophageal sphincter (LES) relaxation (integrated relaxation pressure < upper limit of normal) on esophageal high-resolution manometry (HRM). HE can manifest with dysphagia and chest pain, with unclear mechanisms of symptom generation. The pathophysiology of HE may entail an excessive cholinergic drive with temporal asynchrony of circular and longitudinal muscle contractions; provocative testing during HRM has also demonstrated abnormal inhibition. Hypercontractility can be limited to the esophageal body or can include the LES; rarely, the process is limited to the LES. Hypercontractility can sometimes be associated with esophagogastric junction (EGJ) outflow obstruction and increased muscle thickness. Provocative tests during HRM can increase detection of HE, reproduce symptoms, and predict delayed esophageal emptying. Regarding therapy, an empiric trial of a proton pump inhibitor, should be first considered, given the overlap with gastroesophageal reflux disease. Calcium channel blockers, nitrates, and phosphodiesterase inhibitors have been used to reduce contraction vigor but with suboptimal symptomatic response. Endoscopic treatment with botulinum toxin injection or pneumatic dilation is associated with variable response. Per-oral endoscopic myotomy may be superior to laparoscopic Heller myotomy in relieving dysphagia, but available data are scant. The presence of EGJ outflow obstruction in HE discriminates a subset of patients who may benefit from endoscopic treatment targeting the EGJ., (Copyright © 2020 by The American College of Gastroenterology.)

Background: Motor abnormalities of pharyngeal contraction or upper esophageal sphincter (UES) relaxation can lead to swallowing problems., Methods: We reviewed high-resolution esophageal manometry of children ≤18 years and classified into two groups based on the results of videofluoroscopic study of swallow (VFSS), as normal or abnormal. The UES metrics (integrated relaxation pressure [IRP], resting pressure [URP], and nadir pressure [UNP]), as well as peak pharyngeal pressure (velopharyngeal and meso-hypopharyngeal), were analyzed., Results: UES metrics: There were 142 and 19 subjects in the normal and abnormal groups, respectively. In the normal group, the median UES-IRP at 0.2, 0.4, 0.6, 0.8 seconds, URP, and UNP were 1.0, 4.0, 11.0, 18.0, 53.5, and -1.0 mm Hg while in the abnormal group were 10.0, 13.0, 21.0, 25.5, 47.0, and 8.0 mm Hg. The UES-IRP at 0.2, 0.4, 0.6 seconds, and UNP was significantly higher in the abnormal group. Pharyngeal metrics: We included 58 subjects in normal and 10 subjects in the abnormal group. The median of peak velopharyngeal and meso-hypopharyngeal pressures were lower in the abnormal group; 188.50 vs 210.50, P = .185 and 110.00 vs 144.75 mm Hg, P = .065., Conclusions and Inferences: The UES-IRP was lower than adults, URP was higher than preterm but less than adults, and UNP was lower than neonates but similar to adults. The pharyngeal pressures were higher than those reported for neonates and adults. Our data indicate that motor dynamics of swallowing may change from neonates to adulthood and reflect a maturational process. The subjects with abnormal VFSS had significantly higher UES-IRP and UNP compared to normal VFSS., (© 2020 John Wiley & Sons Ltd.)

Introduction: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO., Methods: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated., Results: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02)., Discussion: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol., (Copyright © 2020 by The American College of Gastroenterology.)

The purpose of this investigation was to review our experience with our comprehensive esophagogastrointestinal transit study in the first 229 patients. This scintigraphic study analyzes the motility of the entire gut, from the esophagus through the rectosigmoid colon. Methods: Data were reviewed for our first 2 y of experience with this examination (184 women and 45 men aged 20-79 y [mean ± SD, 44 ± 16 y]). Patients were referred with symptoms suggestive of a motility disorder. They first swallowed 111 In-diethylenetriaminepentaacetic acid in water for the esophageal-swallow study and then 300 mL for a 30-min 111 In water-only study, followed by 120 mL of 111 In water simultaneously with the solid standardized 99m Tc egg-substitute meal. Images and quantification were obtained for esophageal transit, water-only gastric emptying, water-with-solid gastric emptying, small-bowel transit, and colonic transit. Results: Of the 229 patient studies, 45 (20%) were normal. The remaining 184 (80%) had at least 1 region of dysmotility, for a total of 336 regions of abnormal motility. A single region of dysmotility was seen in 92 patients (50%), 2 regions in 50 (27%), 3 regions in 26 (14%), 4 regions in 12 (7%), and 5 regions in 4 (2%). There was a poor correlation between the results of the water-only study and water with the solid meal. Three different patterns of delayed colonic transit were seen. Patient symptoms were often not predictive of the scintigraphic findings. Conclusion: This study highlights the frequent occurrence of dysmotility in more than 1 region of the gastrointestinal tract in patients with a suspected motility disorder and the frequent concurrence of both upper- and lower-tract dysmotility in the same patients. It provides information to referring physicians regarding which motility disorders may be causing the patient symptoms, why the patient is or is not responding to the present therapy, and if and what additional workup and therapy may be needed., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ., (© 2020 John Wiley & Sons Ltd.)

Esophageal dysphagia is a common symptom in adults. Fluoroscopic contrast studies, endoscopy, and esophageal manometry have been used in the diagnosis of esophageal dysphagia for many years. The diagnostic yield has been improved with new test protocols that highlight abnormal bolus transit in the esophagus and outflow obstruction, as well as new high-definition and high-resolution technical advances in equipment. Functional luminal impedance planimetry and the addition of impedance to high-resolution esophageal manometry have also allowed the assessment of new parameters to better understand esophageal structure and function. In this concise review, we describe the role and utility of various diagnostic modalities in the assessment of patients with esophageal dysphagia., (© 2020 New York Academy of Sciences.)

Introduction: Ineffective esophageal motility (IEM) is a minor motor disorder with potential reflux implications. Contraction reserve, manifested as augmentation of esophageal body contraction after multiple rapid swallows (MRS), may affect esophageal acid exposure time (AET) in IEM., Methods: Esophageal high-resolution manometry (HRM) and ambulatory reflux monitoring studies were reviewed over 2 years to identify patients with normal HRM, IEM (≥50% ineffective swallows), and absent contractility (100% failed swallows). Single swallows and MRS were analyzed using HRM software tools (distal contractile integral, DCI) to determine contraction reserve (mean MRS DCI to mean single swallow DCI ratio >1). Univariate analysis and multivariable regression analyses were performed to determine motor predictors of abnormal AET in the context of contraction reserve., Results: Of 191 eligible patients, 57.1% had normal HRM, 37.2% had IEM, and 5.8% had absent contractility. Contraction reserve had no affect on AET in normal HRM. Nonsevere IEM (5-7 ineffective swallows) demonstrated significantly lower proportions with abnormal AET in the presence of contraction reserve (30.4%) compared with severe IEM (8-10 ineffective swallows) (75.0%, P = 0.03). Abnormal AET proportions in nonsevere IEM with contraction reserve (32.7%) resembled normal HRM (33.0%, P = 0.96), whereas that in severe IEM with (46.2%) or without contraction reserve (50.0%) resembled absent contractility (54.5%, P ≥ 0.6). Multivariable analysis demonstrated contraction reserve to be an independent predictor of lower upright AET in nonsevere (odds ratio 0.44, 95% confidence interval 0.23-0.88) but not severe IEM., Discussion: Contraction reserve affects esophageal reflux burden in nonsevere IEM. Segregating IEM into severe and nonsevere cohorts has clinical value.

Hypercontractile esophagus (HE), also known as jackhammer esophagus, is an esophageal motility disorder. Nowadays, high-resolution manometry (HRM) is used to diagnose the disorder. According to the latest iteration of the Chicago classification, HE is present when at least 2 out 10 liquid swallow-induced peristaltic waves have an abnormally high Distal Contractile Integral. In the era of conventional manometry, a similar condition, referred to as nutcracker esophagus, was diagnosed when the peristaltic contractions had an abnormally high mean amplitude. Although the HRM diagnosis of HE is relatively straight-forward, effective management of the disorder is challenging as the correlation with symptoms is variable and treatment effects are dubious. In this mini-review, we discuss the most troublesome uncertainties that still surround HE, in the light of new data on etiology and epidemiology published in this issue of Neurogastroenterology and Motility., (© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

The functional lumen imaging probe (FLIP) measures luminal dimensions using impedance planimetry, performed most often during sedated upper endoscopy. Mechanical properties of the esophageal wall and opening dynamics of the esophagogastric junction (EGJ) can be objectively evaluated in esophageal motor disorders, eosinophilic esophagitis, esophageal strictures, during esophageal surgery and in postsurgical symptomatic states. Distensibility index, the ratio of EGJ cross sectional area to intraballoon pressure, is the most useful FLIP metric. Secondary peristalsis from balloon distension can be displayed topographically as repetitive anterograde or retrograde contractile activity in the esophageal body, similar to high-resolution manometry. Real-time interpretation and postprocessing of FLIP metadata can complement the identification of esophageal outflow obstruction and achalasia, especially when findings are inconclusive from alternate esophageal tests in symptomatic patients. FLIP can complement the diagnosis of achalasia when manometry and barium studies are inconclusive or negative in patients with typical symptoms. FLIP can direct adequacy of disruption of the EGJ in achalasia when used during and immediately after myotomy and pneumatic dilation. Lumen diameter measured using FLIP in eosinophilic esophagitis and in complex strictures can potentially guide management. An abbreviated modification of the Grading of Recommendations Assessment, Development, and Evaluation was used to determine the quality of available evidence and recommendations regarding FLIP utilization. FLIP metrics that are diagnostic or suggestive of an abnormal motor pattern and metrics that define normal esophageal physiology were developed by consensus and are described in this review.

Background/aims: Jackhammer esophagus (JE) is a hypercontractile esophageal motor disorder defined by at least two swallows with a distal contractile integral (DCI) >8000 mm Hg.s.cm during high-resolution manometry (HRM). The relationship between symptoms and hypercontractility and the response to therapies have been poorly evaluated. The aim of this study was to determine the clinical presentation, manometric diagnosis, and therapeutic results in a large cohort of JE patients., Methods: Patients with JE diagnosed among the HRM tests performed in nine academic French centers from 01/01/2010 to 08/31/2016 were included. Patient charts were reviewed to collect clinical and therapeutic data., Results: Among the 16 264 HRM tests performed during this period, 227 patients (60.8 ± 13.8 years, 151 male) had JE (1.7%). Dysphagia was the most frequent symptom (74.6%), followed by regurgitation (37.1%) and chest pain (36.6%); 4.7% of the patients were asymptomatic. The diagnostic workup was heterogeneous, and only a minority of patients had esophageal biopsies. None of the individual symptoms were significantly associated with any of the manometric parameters defined, except for dysphagia, which was significantly associated with the mean of all DCIs >8000 mm Hg.s.cm (P = .04). Additionally, the number of symptoms was not associated with any manometric parameter. Medical treatment and endoscopic treatments had poor efficacy and a high relapse rate., Conclusion: Jackhammer esophagus is a rare motility disorder. Diagnostic workup is heterogeneous and should be standardized. Symptoms are poorly associated with manometric parameters. The medical treatments and endoscopic therapies currently used are inefficient., (© 2020 John Wiley & Sons Ltd.)

The pathophysiology of jackhammer esophagus is complex and remains unclear. Radiofrequency catheter ablation is indicated for highly symptomatic and drug-refractory atrial fibrillation. This technique can induce esophageal and nerve lesions, due to thermal injury. In this report, we describe a case of hypercontractile esophagus diagnosed by HRM (high-resolution manometry). Esophageal symptoms and HRM normalized immediately after RFCA, and we discuss the pathophysiology of hypercontractile esophagus., (© 2020 John Wiley & Sons Ltd.)