Valdovinos-García, Luis R.

ABSTRACT Recent advances in the diagnosis and management of reflux disease were the central focus of the inaugural Gatherings in Esophagology (GiE), which convened experts across gastroenterology, surgery, otolaryngology, pulmonology, and basic research. The sessions highlighted innovations in reflux monitoring—including high‐resolution manometry, wireless pH monitoring, and novel salivary biomarkers—while critically evaluating their diagnostic accuracy and clinical utility. Presentations explored the limitations of traditional proton‐pump inhibitor therapy, the emergence of potassium‐competitive acid blockers as a new class of acid suppressants, and the evolving role of adjunctive treatments such as mucosal protectants, reflux reducers, and neuromodulators for refractory symptoms. The discourse extended to advanced interventional procedures, including transoral incisionless fundoplication, magnetic sphincter augmentation, and the RefluxStop device, with discussion of patient selection, efficacy, and complication management. Discussants emphasized the pathophysiology and management of extraesophageal manifestations of reflux, the interplay between reflux and pulmonary disease, and the diagnostic challenges in pediatric populations. The meeting also addressed the integration of behavioral therapies, the role of the microbiome, and the application of artificial intelligence in reflux diagnostics. Collectively, these insights underscore a shift toward precision medicine in reflux disease, emphasizing individualized diagnostic strategies and tailored therapeutic approaches to improve patient outcomes.

Summary Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. The normal response to multiple rapid swallows (MRS) is deglutitive inhibition of the esophageal body during the MRS sequence. Our aim was to compare the response to MRS in DES patients and healthy control subjects. Response to MRS during HRM was evaluated in 19 DES patients (8 with and 11 without concomitant esophagogastric junction outflow obstruction [EGJOO]) and 24 asymptomatic healthy controls. Patients with prior gastroesophageal surgery, peroral endoscopic myotomy, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, opioid medication use, and esophageal stricture were excluded. Response to MRS was evaluated for complete versus impaired inhibition (esophageal body contractility with distal contractile integral [DCI] > 100 mmHg-sec-cm during MRS), presence of post-MRS contraction augmentation (DCI post MRS greater than single swallow mean DCI), and integrated relaxation pressure (IRP). Impaired deglutitive inhibition during MRS was significantly more frequent in DES compared to controls (89% vs. 0%, P < 0.001), and frequency was similar for DES with versus without concomitant EGJOO (100% vs. 82%, P = 0.48). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs. 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3360.0 vs. 1238.9, P = 0.009). IRP was lower during MRS compared to single swallows in all patients, and IRP during MRS was normal in 5 of 8 patients with DES and EGJOO. Our study suggests that impaired deglutitive inhibition during MRS is present in the majority of patients with DES regardless of whether they have concomitant EGJOO, and future studies should explore the usefulness of incorporating response to MRS in the diagnosis of DES.

INTRODUCTION: Normal response to multiple rapid swallows (MRS) during high-resolution esophageal manometry is deglutitive inhibition; opioids may interfere with this. The aim of this study was to evaluate the response to MRS in patients on opioids, not on opioids, and healthy controls. METHODS: Response to MRS was evaluated for complete vs impaired inhibition in 72 chronic opioid users, 100 patients not on opioids, and 24 healthy controls. RESULTS: Impaired deglutitive inhibition was significantly more frequent in chronic opioid users compared with patients not on opioids and healthy controls (54% vs 14% vs 0%; P < 0.0001). DISCUSSION: Impaired deglutitive inhibition during MRS is frequent in opioid users, supporting that opioids interfere with esophageal inhibitory signals.

INTRODUCTION: Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during the MRS sequence. We hypothesize that deglutitive inhibition is impaired in DES patients. Aim: compare response to MRS in DES patients and healthy controls. METHODS: Response to MRS was evaluated in 19 DES patients and 24 asymptomatic healthy controls. Demographic and symptom data were extracted from a prospectively maintained motility database. Patients with history of prior gastroesophageal surgery, endoscopic myotomy (POEM), pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, and esophageal stricture were excluded. HRM was performed with a solid state catheter with 36 circumferential pressure sensors 1-cm apart; ten 5-ml liquid swallows were given followed by MRS sequence, analyzed with Manoview software (Medtronic). Esophagogastric junction integrated relaxation pressure (IRP), distal contractile integral (DCI), and distal latency (DL) were calculated, and Chicago Classification v3.0 was applied to diagnose DES (defined by ≥ 2 swallows with DL ≤ 4.5 sec). Response to MRS was evaluated for complete versus impaired inhibition (contractility with DCI > 100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than single-swallow mean DCI). Chi-Square and Fisher’s exact test were used for statistical analysis. RESULTS: Demographics and symptom data are shown in Table 1. Patients with DES were older and more symptomatic than controls. Impaired inhibition of peristalsis during MRS was significantly more frequent in DES compared to controls (89% vs 0%, P < 0.001, Figure 1). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3788 vs 1239, P = 0.013). CONCLUSION: Impaired deglutitive inhibition during MRS is present in the majority of patients with DES, supporting impaired inhibitory pathways in the esophagus as a mechanism of action in this disorder.

INTRODUCTION: We previously showed an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and Jackhammer esophagus. Assessment of response to multiple rapid swallows (MRS) during high-resolution esophageal manometry (HRM) enables detection of impaired inhibition during MRS. Healthy subjects respond to MRS by deglutitive inhibition during MRS followed by an augmented contraction with higher vigor than single swallows. Hypothesis: during MRS, opioids may interfere with deglutitive inhibition and may enhance post MRS contraction. Aim: compare response to MRS in opioid users, non-users and healthy controls. METHODS: Response to MRS was evaluated in 200 patients with esophageal symptoms (100 chronic opioid users on oxycodone, hydrocodone, or tramadol for ≥3 months, 100 not on opioids), and 19 asymptomatic healthy controls that underwent HRM. Patients with prior gastroesophageal surgery, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, esophageal stricture, achalasia type I or II, and scleroderma were excluded. Demographic and symptom data were extracted from a prospectively maintained motility database. Response to MRS was evaluated for complete versus incomplete inhibition (contractility with DCI >100 mmHg-sec-cm during MRS), and presence of post MRS contraction augmentation (DCI post MRS greater than mean DCI for single swallows). Categorical variables were analyzed by chi square. RESULTS: Patients were older than controls (Table 1). HRM indications are shown in Table 2. Incomplete inhibition during MRS was significantly more frequent in chronic opioid users compared to patients not on opioids and healthy controls (26% vs 11% vs 0% P = 0.002; Figure 1). There was a significant difference in the rate of incomplete MRS inhibition for patients on oxycodone, hydrocodone, and tramadol (27% vs 34% vs 22% P = 0.002). The proportion of patients with augmentation post MRS was similar for opioid users, non-opioid users and healthy controls ( P = 0.05). CONCLUSION: Impaired deglutitive inhibition during MRS was significantly more frequent among opioid users compared to non-opioid users and healthy controls. This was more common with stronger opioids (oxycodone and hydrocodone) compared to tramadol. These findings support our hypothesis that opioids interfere with inhibitory signals in the esophagus.

INTRODUCTION: Jackhammer esophagus (JE) is esophageal motility disorder characterized by hypercontractile peristalsis, diagnosed by high resolution manometry (HRM) showing increased contractile vigor distal contractile integral (DCI) >8000 mmHg/s/cm. Hypothesis: hypercontractile peristalsis in JE may be a compensatory mechanism for impaired EGJ relaxation, which even with normal integrated relaxation pressure (IRP), may be expressed as delayed onset of relaxation. We compare time to onset of EGJ relaxation in JE patients with normal IRP, control patients presenting for evaluation of esophageal symptoms with normal HRM, and asymptomatic healthy volunteers. METHODS: We compared time to onset of EGJ relaxation in 44 patients (24 JE, 20 with normal HRM) and 21 asymptomatic healthy volunteers who underwent HRM. Demographic characteristics and validated esophageal questionnaires (GERDQ, BEDQ, Eckardt) collected in all subjects. HRM performed by administering ten 5-ml liquid swallows, Chicago Classification v3.0 used to diagnose JE and normal esophageal motility. Time to onset of EGJ relaxation after swallow initiation was measured in seconds, from time of upper esophageal sphincter opening to EGJ opening. EGJ opening was determined at an isobaric contour of 23 mmHg, based on analysis in the healthy volunteers showing persistent EGJ effacement at this value in 100% of the volunteers. Median times to onset of relaxation for the study groups were compared by Wilcoxon rank sum test. RESULTS: Demographics, questionnaire scores, and HRM metrics in Table 1; patients were older and had higher scores compared to healthy volunteers; HRM metrics were different among the study groups with the exception of DL. Median times to onset of relaxation after swallow initiation shown in Figure 1. There was no difference in median time to onset of relaxation for volunteers compared to patient controls with normal HRM 0.20 s vs 0.90 s, P = 0.149. Median time to onset of relaxation was significantly longer in JE patients compared to volunteers and patient controls 3.30s vs 0.20 s vs 0.90 s, P = 0.001. CONCLUSION: Patients with JE and normal EGJ relaxation by IRP have significantly delayed onset of EGJ relaxation compared to healthy subjects and control patients with normal HRM. Hypercontractile peristalsis in these JE patients could be a compensatory mechanism to overcome outflow obstruction manifested as delayed EGJ relaxation. Therefore, if our findings are confirmed, therapies to address impaired EGJ relaxation could be considered.

INTRODUCTION: High resolution manometry (HRM) is the gold standard to assess esophageal motility. Functional lumen imaging probe topography (FLIP) performed during EGD assesses esophagogastric junction (EGJ) distensibility and esophageal peristalsis. AIM: Evaluate FLIP-HRM agreement and value of FLIP as screening for dysmotility. METHODS: Patients with esophageal symptoms underwent FLIP and HRM. FLIP performed with 16-cm balloon; peristaltic response assessed at 30-40-50-60 ml and classified as repetitive antegrade contractions-RACs, repetitive retrograde contractions-RRCs, diminished/disordered contractility, or absent contractility; median EGJ distensibility index (DI) measured at 60 ml was deemed abnormal (<2 mm 2 /mmHg), indeterminate (2-3 mm 2 /mmHg), normal (> 3 mm 2 /mmHg). Normal FLIP defined by normal EGJ DI and RACs without RRCs. HRM Chicago classification v3.0 diagnosis was dichotomized as normal/minor disorder (normal, ineffective esophageal motility-IEM, or fragmented peristalsis-FP) or abnormal (achalasia, jackhammer esophagus-JE, distal esophageal spasm-DES, EGJ outflow obstruction-EJGOO, absent contractility). FLIP sensitivity/specificity calculated with HRM as gold standard. RESULTS: HRM and FLIP performed a median 18 days apart in 75 patients, 17-92 yo, 65% F. HRM diagnoses: normal/minor disorder 45% (28% normal, 16% IEM, 1% FP), abnormal 55% (17% absent contractility, 16% achalasia, 15 % EGJOO, 4% JE, 3% DES). FLIP diagnoses: 33% normal, 77% abnormal. When FLIP was normal, HRM showed normal/minor disorder in 58% (53% normal, 5% IEM), absent contractility 26%, JE 11%, EGJOO 5% (no achalasia or DES). Normal FLIP had 80% specificity for normal/minor HRM disorder. When FLIP was abnormal, HRM showed achalasia 21%, normal 20%, IEM 19%, EGOO 18%, absent contractility 14%, DES 4%, JE 2%, FP 2%. FLIP had 80% sensitivity for major motility disorder on HRM and was abnormal in 100% patients with achalasia or DES. A normal EGJ DI by itself had a negative predictive value of 90% for normal/minor HRM disorder. CONCLUSION: FLIP topography performed during EGD is promising as a screening tool for esophageal dysmotility, with 80% specificity for normal/minor HRM disorder, and 80% sensitivity for major HRM disorder. Normal FLIP during EGD for evaluation of esophageal symptoms may obviate the need for manometry. Likewise, HRM is clearly indicated in patients with abnormal FLIP, with high likelihood of major motility disorder on HRM in these patients.