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2-year follow-up data from our randomised controlled trial showed that peroral endoscopic myotomy is associated with a significantly higher efficacy than pneumatic dilation as initial treatment of therapy-naive patients with achalasia. Here we report therapeutic success rates in patients treated with peroral endoscopic myotomy compared with pneumatic dilation at the 5-year follow-up.We did a multicentre, randomised controlled trial in six hospitals in the Netherlands, Germany, Italy, Hong Kong, and the USA. Adults aged 18-80 years with newly diagnosed symptomatic achalasia (based on an Eckardt score3) were eligible for inclusion. Patients were randomly assigned (1:1) to peroral endoscopic myotomy or pneumatic dilation using web-based randomisation with a random block size of 8 and stratification according to site. Randomisation concealment for treatment type was double blind until official study enrolment. Treatment was unmasked because of the different technical approach of each procedure. Patients in the pneumatic dilation group were dilated with a single series of 30-35 mm balloons. The need for subsequent dilations in the pneumatic dilation group, and the need for dilation after initial treatment in the peroral endoscopic myotomy group, was considered treatment failure. The primary outcome was therapeutic success (Eckardt score ≤3 in the absence of severe treatment-related complications and no need for retreatment). Analysis of the primary outcome was by modified intention to treat, including all patients randomly assigned to a group, excluding those patients who did not receive treatment or were lost to follow-up. Safety was assessed in all included patients. This study is registered at the Dutch Trial Registry, NTR3593, and is completed.Between Sept 21, 2012, and July 20, 2015, 182 patients were assessed for eligibility, 133 of whom were included in the study and randomly assigned to peroral endoscopic myotomy (n=67) or pneumatic dilation (n=66). 5-year follow-up data were available for 62 patients in the peroral endoscopic myotomy group and 63 patients in the pneumatic dilation group. 50 (81%) patients in the peroral endoscopic myotomy group had treatment success at 5 years, compared with 25 (40%) in the pneumatic dilation group, an adjusted absolute difference of 41% (95% CI 25-57; p0·0001). Reasons for failure were no initial effect of treatment (one patient in the peroral endoscopic myotomy group vs 12 patients in the pneumatic dilation group) and recurrent symptoms causing treatment failure (11 patients in the peroral endoscopic myotomy group [seven patients between 2 and 5 years] vs 25 patients in the pneumatic dilation group [nine patients between 2 and 5 years]); one patient in the pneumatic dilation group had treatment failure due to an adverse event. Proton-pump inhibitor use (mostly daily) was significantly higher after peroral endoscopic myotomy than after pneumatic dilation among patients still in clinical remission (23 [46%] of 50 patients vs three [13%] of 24 patients; p=0·008). 5-year follow-up endoscopy of patients still in clinical remission showed reflux oesophagitis in 14 (33%) of 42 patients in the peroral endoscopic myotomy group (12 [29%] grade A or B, two [5%] grade C or D) and two (13%) of 16 patients in the pneumatic dilation group (two [13%] grade A or B, none grade C or D; p=0·19). No intervention-related serious adverse events occurred between 2 and 5 years after treatment. The following non-intervention-related serious adverse events occurred between 2 and 5 years: a stroke (one [2%]) in the peroral endoscopic myotomy group; and death due to a melanoma (one [2%]) and dementia (one [2%]) in the pneumatic dilation group.Based on this study, peroral endoscopic myotomy should be proposed as an initial treatment option for patients with achalasia. Although our study has shown that peroral endoscopic myotomy has greater long-term efficacy with a low risk of major treatment-related complications, this should not lead to abandonment of pneumatic dilation from clinical practice. Ideally, all treatment options should be discussed with treatment-naive patients with achalasia and a shared decision should be made.Fonds NutsOhra and European Society of Gastrointestinal Endoscopy.

Esophagogastric junction (EGJ) outflow obstruction (EGJOO) per Chicago Classification v4.0 (CCv4.0) represents a high-resolution manometry (HRM) diagnosis with uncertain clinical significance. This study aimed to evaluate functional lumen imaging probe (FLIP) panometry among patients with EGJOO on HRM/CCv4.0 to assess clinical/manometric associations and treatment outcomes.An observational cohort study was performed on patients who completed FLIP during endoscopy and had an HRM/CCv4.0 diagnosis of EGJOO, i.e., HRM-EGJOO (inconclusive). Abnormal FLIP panometry motility classifications were applied to identify FLIP-confirmed conclusive EGJOO. Rapid drink challenge on HRM and timed barium esophagram were also assessed. Clinical management plan was determined by treating physicians and assessed through chart review. Clinical outcome was defined using the Eckardt score (ES) during follow-up evaluation: ES3 was considered a good outcome.Of 139 adult patients with manometric EGJOO (inconclusive per CCv4.0), a treatment outcome ES was obtained in 55 after achalasia-type treatment (i.e., pneumatic dilation, peroral endoscopic myotomy, laparoscopic Heller myotomy, or botulinum toxin injection) and 36 patients after other nonachalasia-type treatment. Among patients with conclusive EGJOO by HRM-FLIP complementary impression, 77% (33/43) had a good outcome after achalasia-type treatment, whereas 0% (0/12) of patients had a good outcome after nonachalasia-type treatment. Of patients with normal EGJ opening on FLIP, one-third of patients treated with achalasia-type treatment had a good outcome, while 9 of the 10 treated conservatively had a good outcome.FLIP panometry provides a useful complement to clarify the clinical significance of an HRM/CCv4.0 EGJOO diagnosis and help direct management decisions.

BACKGROUND & AIMS: This study aimed to assess the accuracy of functional luminal imaging probe (FLIP) Panometry to detect esophagogastric junction (EGJ) obstruction assigned by high-resolution manometry (HRM) and the Chicago Classification version 4.0 (CCv4.0). METHODS: 687 adult patients that completed FLIP and HRM for primary esophageal motility evaluation and 35 asymptomatic volunteers (“controls”) were included. EGJ opening was evaluated with 16-cm FLIP during sedated endoscopy via EGJ-distensibility index (DI) and maximum EGJ diameter. HRM was classified according to CCv4.0 and focused on studies with a conclusive disorder of EGJ outflow (i.e. achalasia subtypes I, II, or III; or EGJ outflow obstruction with abnormal timed barium esophagram) or normal EGJ outflow. RESULTS: All 35 controls had EGJ-DI >3.0mm(2)/mmHg and maximum EGJ diameter >16mm. Per HRM and CCv4.0, 245 patients had a conclusive disorder of EGJ outflow and 314 patients had normal EGJ outflow. Among the 241 patients with reduced EGJ opening (REO: EGJ-DI

BACKGROUND & AIMS: 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: 539 adult patients that completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. 35 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 to distension (i.e. secondary peristalsis) were evaluated with 16-cm FLIP performed during sedated endoscopy and analyzed using a customize 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 (NEO) and a normal or borderline contractile response; 95% of these patients had normal motility or ineffective esophageal motility on HRM. 202 patients (37%) had obstruction with weak contractile response, defined as reduced EGJ opening and absent contractile response or impaired/disordered contractile response, on FLIP Panometry; 92% of these patients had a disorder of EGJ outflow per CCv4.0. CONCLUSIONS: 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 provides a well-tolerated method that can complement, or in some cases be an alternative to HRM, for evaluating esophageal motility disorders.

Introduction High-resolution manometry (HRM) is generally considered the primary method to evaluate esophageal motility; functional luminal imaging probe (FLIP) panometry represents a novel method to do so and is completed during sedated endoscopy. This study aimed to compare HRM and FLIP panometry in predicting esophageal retention on timed barium esophagram (TBE). Methods A total of 329 adult patients who completed FLIP, HRM, and TBE for primary esophageal motility evaluation were included. An abnormal TBE was defined by a 1-minute column height >5 cm or impaction of a 12.5-mm barium tablet. The integrated relaxation pressure (IRP) on HRM was assessed in the supine and upright patient positions. Esophagogastric junction (EGJ) opening was evaluated with 16-cm FLIP performed during sedated endoscopy through EGJ-distensibility index and maximum EGJ diameter. Results Receiver operating characteristic curves to identify an abnormal TBE demonstrated AUC (95% confidence interval) of 0.79 (0.75-0.84) for supine IRP, 0.79 (0.76-0.86) for upright IRP, 0.84 (0.79-0.88) for EGJ-distensibility index, and 0.88 (0.85-0.92) for maximum EGJ diameter. Logistic regression to predict abnormal TBE showed odds ratios (95% confidence interval) of 1.8 (0.84-3.7) for consistent IRP elevation and 39.7 (16.4-96.2) for reduced EGJ opening on FLIP panometry. Of 40 patients with HRM-FLIP panometry discordance, HRM-IRP was consistent with TBE in 23% while FLIP panometry was consistent with TBE in 78%. Discussion FLIP panometry provided superior detection of esophageal retention over IRP on HRM. However, application of a complementary evaluation involving FLIP panometry, HRM, and TBE may be necessary to accurately diagnose esophageal motility disorders.

Background Proton pump inhibitors (PPIs) are widely used to treat and prevent acid-related disorders. Despite high efficacy, PPI safety has been increasingly scrutinised. However, no comprehensive review summarising investigations of various adverse events is available. Aims To perform an umbrella review to comprehensively assess associations between adverse events and PPI use. Methods In accordance with PRISMA, an umbrella review of systematic reviews with meta-analyses was conducted. PubMed and EMBASE were searched from 2015 to July 2019. AMSTAR 2 and GRADE were used to assess quality and certainty of evidence. Author-reported quality assessments were also reviewed. Results Forty-two systematic reviews with meta-analyses, supported predominantly by observational evidence, were included. The most comprehensive studies reported statistically significant associations with PPI use for several outcomes, including: fractures (eg, hip; RR = 1.20; 95% CI = 1.14-1.28; n = 2 103 800), kidney disease (eg, acute kidney injury; RR = 1.61; 95% CI = 1.16-2.22; n = 2 396 640), infections (eg, Clostridioides difficile; OR = 1.99; 95% CI = 1.73-2.30; n = 356 683), gastric cancer (OR = 2.50; 95% CI = 1.74-3.85; n = 943 070) and gastrointestinal events (eg, fundic gland polyps; OR = 2.46; 95% CI = 1.42-4.27; n = 40 218). No associations with non-gastric cancers, or neurological disease were concluded, with conflicting evidence for cardiovascular outcomes. Certainty based on GRADE was very low for most outcomes. Conclusions This review identified several published associations between PPIs and adverse outcomes, however, further investigation is needed to understand their clinical significance and the likelihood of causal relationship. If higher quality evidence is generated substantiating the potential risks, it may be necessary for clinicians to consider alternative treatment strategies, especially when PPI efficacy is suboptimal.

Achalasia is a debilitating major motor disorder of the oesophagus. Hypervigilance and symptom-specific anxiety substantially impact dysphagia symptom reporting, and quality of life is a critical patient outcome. Earlier achalasia symptom scales did not consider these constructs in their psychometric development.To develop a new symptom measure, the Achalasia Patient-Reported Outcomes (APRO) Questionnaire METHODS: Four gastroenterologists with achalasia expertise generated preliminary items. Patients reviewed items via cognitive interviews. Patients undergoing high-resolution manometry completed the APRO with Oesophageal Hypervigilance and Anxiety Scale, Northwestern Oesophageal Quality of Life Scale, and three measures of reflux and dysphagia. Full APRO psychometric assessment (reliability, validity, factor structure) was done. Cluster analysis evaluated APRO + symptom-anxiety/hypervigilance patient phenotypes.We included 961 patients with normal motility and 296 with achalasia. The APRO yielded three subscales: dysphagia, reflux, chest pain with two items for weight change and diet modifications. Reliability and validity were excellent. Twenty-five percent of achalasia patients may have high levels of anxiety/hypervigilance despite low symptoms, while 8% may report severe symptoms with low anxiety/hypervigilance. The APRO significantly predicted quality of life, but less cognitive-affective processes.The APRO is a reliable and valid measure of achalasia symptoms that addresses the limitations of existing questionnaires. Symptom anxiety and hypervigilance moderate the relationship between APRO and quality of life; 33% of patients with achalasia exhibit concerning patterns in symptom severity, anxiety and hypervigilance that may contribute to poorer outcomes.

A unique motor response to sustained esophageal distension, repetitive antegrade contractions (RACs), is observed using functional luminal imaging probe (FLIP) panometry. However, physiologic mechanisms related to this response are unexplored. This study aimed to evaluate the impact of cholinergic inhibition with atropine on the esophageal contractile response to sustained distention, including RACs, among healthy volunteers.8 asymptomatic volunteers (ages 22-45) were evaluated in a crossover study design with 16-cm FLIP positioned across the esophagogastric junction and distal esophagus during sedated upper endoscopy. The FLIP study involving stepwise volumetric distension was performed twice in each subject, at baseline and again after atropine (15 mcg/kg) was administered intravenously. FLIP panometry was analyzed to assess the contractile response to distension.Antegrade contractions, lumen-occluding contractions, and a RAC pattern were observed in 8/8, 8/8, and 7/8(88%) subjects, respectively, at baseline and in 5/8 (63%), 2/8 (25%) and 2/8 (25%) subjects after atropine. The rate of contractions in the RAC pattern was similar (6-7 contractions per minute) before and after atropine. Compared with the baseline study, distension-induced contractility was triggered at higher fill volumes after atropine. FLIP pressures were lower in response to volumetric filling after atropine than at baseline.The vigor and triggering of the esophageal contractile response to distension is reduced by cholinergic inhibition in asymptomatic controls. The observation that the rate of contractions did not change when patients developed repetitive contractile responses suggests that this rate is not modified by cholinergic inhibition once contractility is triggered.

OBJECTIVES Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM. METHODS Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM. RESULTS Two hundred thirty-six patients, aged 18-85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (Radj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: Radj = 0.118 (P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant. DISCUSSION In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

We used in silico models to investigate the impact of the dimensions of myotomy, contraction pattern, the tone of the esophagogastric junction (EGJ), and musculature at the myotomy site on esophageal wall stresses potentially leading to the formation of a blown-out myotomy (BOM). We performed three sets of simulations with an in silico esophagus model, wherein the myotomy-influenced region was modeled as an elliptical section devoid of muscle fibers. These sets investigated the effects of the dimensions of myotomy, differing esophageal contraction types, and differing esophagogastric junction (EGJ) tone and wall stiffness at the myotomy affected region on esophageal wall stresses potentially leading to BOM. Longer myotomy was found to be accompanied by a higher bolus volume accumulated at the myotomy site. With respect to esophageal contractions, deformation at the myotomy site was greatest with propagated peristalsis, followed by combined peristalsis and spasm, and pan-esophageal pressurization. Stronger EGJ tone with respect to the wall stiffness at the myotomy site was found to aid in increasing deformation at the myotomy site. In addition, we found that an esophagus with a shorter myotomy performed better at emptying the bolus than that with a longer myotomy. Shorter myotomies decrease the chance of BOM formation. Propagated peristalsis with EGJ outflow obstruction has the highest chance of BOM formation. We also found that abnormal residual EGJ tone may be a co-factor in the development of BOM, whereas remnant muscle fibers at myotomy site reduce the risk of BOM formation. NEW & NOTEWORTHY Blown-out myotomy (BOM) is a complication observed after myotomy, which is performed to treat achalasia. In silico simulations were performed to identify the factors leading to BOM formation. We found that a short myotomy that is not transmural and has some structural architecture intact reduces the risk of BOM formation. In addition, we found that high esophagogastric junction tone due to fundoplication is found to increase the risk of BOM formation.

Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response.This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks.Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01).This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

An association of eosinophilic esophagitis (EoE) with esophageal dysmotility has been described, however, the related mechanism remains unclear. We aimed to evaluate clinical and physiologic characteristics, including esophageal distensibility, associated with secondary peristalsis in patients with EoE.A total of 199 consecutive adult patients with EoE (age, 18-78 y; 32% female) who completed a 16-cm functional luminal imaging probe (FLIP) during endoscopy were evaluated in a cross-sectional study. FLIP panometry contractile response (CR) patterns were classified as normal CR or borderline CR if antegrade contractions were present, and abnormal CRs included impaired/disordered CR, absent CR, or spastic-reactive CR. The distensibility plateau of the esophageal body and esophagogastric junction distensibility was measured with FLIP.FLIP CR patterns included 68 (34%) normal CR, 65 (33%) borderline CR, 44 (22%) impaired/disordered CR, 16 (8%) absent CR, and 6 (3%) spastic-reactive CR. Compared with normal CRs, abnormal CRs more frequently had reduced esophageal distensibility (distensibility plateau17 mm in 56% vs 32%), greater total EoE reference scores (median, 5; interquartile range [IQR], 3-6 vs median, 4; IQR, 3-5) with more severe ring scores, and a greater duration of symptoms (median, 10 y; IQR, 4-23 y vs median, 7 y; IQR, 3-15 y). Mucosal eosinophil density, however, was similar between abnormal CRs and normal CRs (median, 34 eosinophils/high-power field [hpf]; IQR, 14-60 eosinophils/hpf vs median, 25 eosinophils/hpf; IQR, 5-50 eosinophils/hpf).Although normal secondary peristalsis was observed frequently in this EoE cohort, abnormal esophageal CRs were related to EoE disease severity, especially features of fibrostenosis. This study evaluating secondary peristalsis in EoE suggests that esophageal wall remodeling, rather than eosinophilic inflammatory intensity, was associated with esophageal dysmotility in EoE.

To compare the utility of the distensibility index (DI) on functional lumen imaging probe (FLIP) topography to other esophagogastric junction (EGJ) metrics in assessing treatment response in achalasia in the context of esophageal anatomy.We prospectively evaluated 79 patients (at ages 17-81 years; 47% female patients) with achalasia during follow-up after pneumatic dilation, Heller myotomy, or per-oral endoscopic myotomy with timed barium esophagram, high-resolution impedance manometry, and FLIP. Anatomic deformities were identified based on consensus expert opinion. Patients were classified based on anatomy and EGJ opening to determine the association with radiographic outcome and Eckardt score (ES).Twenty-seven patients (34.1%) had an anatomic deformity-10 pseudodiverticula at myotomy, 7 epiphrenic diverticula, 5 sigmoid, and 5 sinktrap. A 5-minute column area of5 cm was best associated with an ES of3, with a sensitivity of 84% (P = 0.0013). Area under the curve for EGJ metrics in association with retention was as follows: DI, 0.90; maximal EGJ diameter, 0.76; integrated relaxation pressure, 0.64; and basal esophagogastric junction pressure, 0.53. Only FLIP metrics were associated with retention given normal anatomy (DI 2.4 vs 5.2 mm/mm Hg and maximal EGJ diameter 13.1 vs 16.6 mm in patients with and without retention, respectively; P values0.0001 and 0.002). Using a DI cutoff of2.8 as abnormal, 40 of 45 patients with retention (P = 0.0001) and 23 of 25 patients with an ES of3 (P = 0.02) had a low DI and/or anatomic deformity. With normal anatomy, 21 of 22 patients with retention had a low or borderline low DI.The FLIP DI is most useful metric for assessing the effect of achalasia treatment on EGJ opening. However, abnormal anatomy is an important mediator of outcome and treatment success will be modulated by anatomic defects that impede bolus emptying.

In this study, we quantify the work done by the esophagus to open the esophagogastric junction (EGJ) and create a passage for bolus flow into the stomach. Work done on the EGJ was computed using functional lumen imaging probe (FLIP) panometry. Eighty-five individuals underwent FLIP panometry with a 16-cm catheter during sedated endoscopy including asymptomatic controls (n = 14), 45 patients with achalasia (n = 15 each, three subtypes), those with gastroesophageal reflux disease (GERD; n = 13), those with eosinophilic esophagitis (EoE; n = 8), and those with systemic sclerosis (SSc; n = 5). Luminal cross-sectional area (CSA) and pressure were measured by the FLIP catheter positioned across the EGJ. Work done on the EGJ (EGJW) was computed (millijoules, mJ) at 40-mL distension. Additionally, a separate method was developed to estimate the “work required” to fully open the EGJ (EGJROW) when it did not open during the procedure. EGJW for controls had a median [interquartile range (IQR)] value of 75 (56–141) mJ. All achalasia subtypes showed low EGJW compared with controls (P < 0.001). Subjects with GERD and EoE had EGJW 54.1 (6.9–96.3) and 65.9 (10.8–102.3) mJ, similar to controls (P < 0.08 and P < 0.4, respectively). The scleroderma group showed low values of EGJW, 12 mJ (P < 0.001). For patients with achalasia, EGJROW was the greatest and had a value of 210.4 (115.2–375.4) mJ. Disease groups with minimal or absent EGJ opening showed low values of EGJW. For patients with achalasia, EGJROW significantly exceeded EGJW values of all other groups, highlighting its unique pathophysiology. Balancing the relationship between EGJW and EGJROW is potentially useful for calibrating achalasia treatments and evaluating treatment response. NEW & NOTEWORTHY Changes in pressure and diameter occur at the EGJ during esophageal emptying. Similar changes can be observed during FLIP panometry. Data from healthy and diseased individuals were used to estimate the mechanical work done on the EGJ during distension-induced relaxation or, in instances of failed opening, work required to open the EGJ. Quantifying these parameters is potentially valuable to calibrate treatments and gauge treatment efficacy for subjects with disorders of EGJ function, especially achalasia.

Background Despite widespread adoption of potent acid suppression treatment with proton pump inhibitors (PPI) for reflux-like symptoms, persistent symptoms are commonly reported in primary care and community studies. Aims This multidisciplinary review critically evaluates how the management of reflux-like symptoms could better reflect their multifactorial pathophysiology. Methods A panel of experts (from general practice, gastroenterology and gastropsychology) attended a series of workshops to review current management and propose a framework for the provision of more individualised care. Results It was agreed that the perceptual (as well as the physiological) causes of reflux-like symptoms should be considered at the start of management, not as a last resort when all else has failed. A short course of PPI is a pragmatic approach to address reflux-like symptoms, but equally important is counselling about the gut-brain axis and provision of symptom-specific behavioural interventions for those who show signs of somatisation, hypervigilance or co-existing disorders of gut-brain interaction. Other low-harm interventions such as lifestyle and dietary advice, should also be better integrated into care at an early stage. Multidisciplinary care management programmes (including dietary, weight loss, exercise and behavioural intervention) should be developed to promote greater self-management and take advantage of the general shift toward the use of remotely accessed health care resources. Conclusions Management of reflux-like symptoms should be adapted to reflect the advances in knowledge about the multifactorial aetiology of these symptoms, addressing both acid-related and behavioural components early in management. The time has come to treat the patient, not the "disease".

BACKGROUND & AIMS: As many as one-half of all patients with suspected gastroesophageal reflux disease (GERD) do not derive benefit from acid suppression. This review outlines a personalized diagnostic and therapeutic approach to GERD symptoms. METHODS: The Best Practice Advice statements presented here were developed from expert review of existing literature combined with extensive discussion and expert opinion to provide practical advice. Formal rating of the quality of evidence or strength of recommendations was not the intent of this clinical practice update. BEST PRACTICE ADVICE 1: Clinicians should develop a care plan for investigation of symptoms suggestive of GERD, selection of therapy (with explanation of potential risks and benefits), and long-term management, including possible de-escalation, in a shared-decision making model with the patient. BEST PRACTICE ADVICE 2: Clinicians should provide standardized educational material on GERD mechanisms, weight management, lifestyle and dietary behaviors, relaxation strategies, and awareness about the brain-gut axis relationship to patients with reflux symptoms. BEST PRACTICE ADVICE 3: Clinicians should emphasize safety of proton pump inhibitors (PPIs) for the treatment of GERD. BEST PRACTICE ADVICE 4: Clinicians should provide patients presenting with troublesome heartburn, regurgitation, and/ or non-cardiac chest pain without alarm symptoms a 4- to 8-week trial of single-dose PPI therapy. With inadequate response, dosing can be increased to twice a day or switched to a more effective acid suppressive agent once a day. When there is adequate response, PPI should be tapered to the lowest effective dose. BEST PRACTICE ADVICE 5: If PPI therapy is continued in a patient with unproven GERD, clinicians should evaluate the appropriateness and dosing within 12 months after initiation, and offer endoscopy with prolonged wireless reflux monitoring off PPI therapy to establish appropriateness of long-term PPI therapy. BEST PRACTICE ADVICE 6: If troublesome heartburn, regurgitation, and/or non-cardiac chest pain do not respond adequately to a PPI trial or when alarm symptoms exist, clinicians should investigate with endoscopy and, in the absence of erosive reflux disease (Los Angeles B or greater) or long-segment (≥3 cm) Barrett’s esophagus, perform prolonged wireless pH monitoring off medication (96-hour preferred if available) to confirm and phenotype GERD or to rule out GERD. BEST PRACTICE ADVICE 7: Complete endoscopic evaluation of GERD symptoms includes inspection for erosive esophagitis (graded according to the Los Angeles classification when present), diaphragmatic hiatus (Hill grade of flap valve), axial hiatus hernia length, and inspection for Barrett’s esophagus (graded according to the Prague classification and biopsied when present). BEST PRACTICE ADVICE 8: Clinicians should perform upfront objective reflux testing off medication (rather than an empiric PPI trial) in patients with isolated extra-esophageal symptoms and suspicion for reflux etiology. BEST PRACTICE ADVICE 9: In symptomatic patients with proven GERD, clinicians should consider ambulatory 24-hour pHimpedance monitoring on PPI as an option to determine the mechanism of persisting esophageal symptoms despite therapy (if adequate expertise exists for interpretation). BEST PRACTICE ADVICE 10: Clinicians should personalize adjunctive pharmacotherapy to the GERD phenotype, in contrast to empiric use of these agents. Adjunctive agents include alginate antacids for breakthrough symptoms, nighttime H2 receptor antagonists for nocturnal symptoms, baclofen for regurgitation or belch predominant symptoms, and prokinetics for coexistent gastroparesis. BEST PRACTICE ADVICE 11: Clinicians should provide pharmacologic neuromodulation, and/or referral to a behavioral therapist for hypnotherapy, cognitive behavioral therapy, diaphragmatic breathing, and relaxation strategies in patients with functional heartburn or reflux disease associated with esophageal hypervigilance reflux hypersensitivity and/or behavioral disorders. BEST PRACTICE ADVICE 12: In patients with proven GERD, laparoscopic fundoplication and magnetic sphincter augmentation are effective surgical options, and transoral incisionless fundoplication is an effective endoscopic option in carefully selected patients. BEST PRACTICE ADVICE 13: In patients with proven GERD, Roux-en-Y gastric bypass is an effective primary anti-reflux intervention in obese patients, and a salvage option in non-obese patients, whereas sleeve gastrectomy has potential to worsen GERD. BEST PRACTICE ADVICE 14: Candidacy for invasive anti-reflux procedures includes confirmatory evidence of pathologic GERD, exclusion of achalasia, and assessment of esophageal peristaltic function.

The goal of this study was to conceptualize and compute measures of “mechanical work” done by the esophagus using data generated during functional lumen imaging probe (FLIP) panometry and compare work done during secondary peristalsis among patients and controls. Eighty-five individuals were evaluated with a 16-cm FLIP during sedated endoscopy, including asymptomatic controls (n = 14) and those with achalasia subtypes I, II, and III (n = 15, each); gastroesophageal reflux disease (GERD; n = 13); eosinophilic esophagitis (EoE; n = 9); and systemic sclerosis (SSc; n = 5). The FLIP catheter was positioned to have its distal segment straddling the esophagogastric junction (EGJ) during stepwise distension. Two metrics of work were assessed: “active work” (during bag volumes ≤ 40 mL where contractility generates substantial changes in lumen area) and “work capacity” (for bag volumes ≥ 60 mL when contractility cannot substantially alter the lumen area). Controls showed median [interquartile range (IQR)] of 7.3 (3.6–9.2) mJ of active work and 268.6 (225.2–332.3) mJ of work capacity. Patients with all achalasia subtypes, GERD, and SSc showed lower active work done than controls (P ≤ 0.003). Patients with achalasia subtypes I and II, GERD, and SSc had lower work capacity compared with controls (P < 0.001, 0.004, 0.04, and 0.001, respectively). Work capacity was similar between controls and patients with achalasia type III and EoE. Mechanical work of the esophagus differs between healthy controls and patient groups with achalasia, EoE, SSc, and GERD. Further studies are needed to fully explore the utility of this approach, but these work metrics would be valuable for device design (artificial esophagus), to measure the efficacy of peristalsis, to gauge the physiological state of the esophagus, and to comment on its pumping effectiveness. NEW & NOTEWORTHY Functional lumen imaging probe (FLIP) panometry assesses esophageal response to distension and provides a simultaneous assessment of pressure and dimension during contractility. This enables an objective assessment of “mechanical work” done by the esophagus. Eighty-five individuals were evaluated, and two work metrics were computed for each subject. Controls showed greater values of work compared with individuals with achalasia, gastroesophageal reflux disease (GERD), and systemic sclerosis (SSc). These values can quantify the mechanical behavior of the distal esophagus and assist in the estimation of muscular integrity.

Background and Aims Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs. Methods This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD). Results Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, –43.7% vs –5.3%; P = .04). Conclusions Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537)

The widespread adoption of high-resolution manometry (HRM) has led to a restructuring in the classification of esophageal motility disorder classification summarized in the Chicago Classification, currently in version 3.0. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or even with preserved peristalsis. Furthermore, despite these advances in diagnostics, no single manometric pattern is perfectly sensitive or specific for idiopathic achalasia and complimentary assessments with provocative maneuvers during HRM or interrogating the esophagogastric junction with the functional luminal imaging probe during endoscopy can be useful in clarifying equivocal or inexplicable HRM findings. Using these tools, we have come to conceptualize esophageal motility disorders as characterized by obstructive physiology at the esophagogastric junction, smooth muscle esophagus, or both. Recognizing obstructive physiology as a primary target of therapy has become particularly relevant with the development of a minimally invasive technique for performing a calibrated myotomy of the esophageal circular muscle, the POEM procedure. Now and going forward, optimal management is to render treatment in a phenotype-specific manner: e.g. POEM calibrated to patient-specific physiology for spastic achalasia and spastic disorders of the smooth muscle esophagus, more conservative strategies (pneumatic dilation) for the disorders limited to the sphincter.

Background & Aims A normal esophageal response to distension on functional luminal imaging probe (FLIP) panometry during endoscopy might indicate normal esophageal motor function. We aimed to investigate the correlation of normal FLIP panometry findings with esophageal high-resolution manometry (HRM) and outcomes of discrepant patients. Methods We performed a retrospective study using data from a registry of patients who completed FLIP during sedated endoscopy. We identified 111 patients with normal FLIP panometry findings (mean age, 42 y; 69% female) and corresponding HRM data. A normal FLIP panometry was defined as an esophagogastric junction (EGJ) distensibility index greater than 3.0 mm2/mm Hg, an absence of repetitive retrograde contractions, and a repetitive antegrade contraction pattern that met the Rule-of-6s: ≥6 consecutive antegrade contractions of ≥6-cm in length, at a rate of 6 ± 3 contractions per minute. HRM findings were classified by the Chicago classification system version 3.0. Results HRM results were classified as normal motility in 78 patients (70%), ineffective esophageal motility in 10 patients (9%), EGJ outflow obstruction in 20 patients (18%), and 3 patients (3%) as other. In patients with EGJ outflow obstruction based on HRM, the integrated relaxation pressure normalized on adjunctive swallows in 16 of 20 patients (80%), and in 8 of 9 patients (88%) who completed a barium esophagram and had normal barium clearance. Thus, although 23 of 111 patients (21%) with normal FLIP panometry had abnormal HRM findings, these HRMs often were considered to be false-positive or equivocal results. All patients with an abnormal result from HRM were treated conservatively. Conclusions In a retrospective cohort study, we found that patients with normal FLIP panometry results did not have a clinical impression of a major esophageal motor disorder. Normal FLIP panometry results can exclude esophageal motility disorders at the time of endoscopy, possibly negating the need for HRM in select patients.

BACKGROUND: The aim of this study was to assess expert gastroenterologists’ opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. METHODS: Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. RESULTS: Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: histamine-2 receptor antagonists for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association. CONCLUSION: For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies were preferred for all other scenarios.

Symptoms related to abnormal gastrointestinal motility and function are common. Oropharyngeal and oesophageal dysphagia, heartburn, bloating, abdominal pain and alterations in bowel habits are among the most frequent reasons for seeking medical attention from internists or general practitioners and are also common reasons for referral to gastroenterologists and colorectal surgeons. However, the nonspecific nature of gastrointestinal symptoms, the absence of a definitive diagnosis on routine investigations (such as endoscopy, radiology or blood tests) and the lack of specific treatments make disease management challenging. Advances in technology have driven progress in the understanding of many of these conditions. This Review serves as an introduction to a series of Consensus Statements on the clinical measurements of gastrointestinal motility, function and sensitivity. A structured, evidence-based approach to the initial assessment and empirical treatment of patients presenting with gastrointestinal symptoms is discussed, followed by an outline of the contribution of modern physiological measurement on the management of patients in whom the cause of symptoms has not been identified with other tests. Discussions include the indications for and utility of high-resolution manometry, ambulatory pH-impedance monitoring, gastric emptying studies, breath tests and investigations of anorectal structure and function in day-to-day practice and clinical management.

Repetitive retrograde contractions (RRCs) in response to sustained esophageal distension are a distinct contractility pattern observed with functional luminal imaging probe (FLIP) panometry that are common in type III (spastic) achalasia. RRCs are hypothesized to be indicative of either impaired inhibitory innervation or esophageal outflow obstruction. We aimed to apply FLIP panometry to patients with postfundoplication dysphagia (a model of esophageal obstruction) to explore mechanisms behind RRCs. Adult patients with dysphagia after Nissen fundoplication ( n = 32) or type III achalasia ( n = 25) were evaluated with high-resolution manometry (HRM) and upper endoscopy with FLIP. HRM studies were assessed for outflow obstruction and spastic features: premature contractility, hypercontractility, and impaired deglutitive inhibition during multiple-rapid swallows. FLIP studies were analyzed to determine the esophagogastric junction (EGJ)-distensibility index and contractility pattern, including RRCs. Barium esophagram was evaluated when available. RRCs were present in 8/32 (25%) fundoplication and 19/25 (76%) achalasia patients ( P < 0.001). EGJ outflow obstruction was detected in 21 (67%) fundoplication patients by HRM, FLIP, or esophagram [6 (29%) had RRCs]. On HRM, none of the fundoplication patients had premature contractility, whereas 3/4 with defective inhibition on multiple-rapid swallows and 2/4 with hypercontractility had RRCs. Regression analysis demonstrated HRM with spastic features, but not esophageal outflow obstruction, as a predictor for RRCs. RRCs in response to sustained esophageal distension appear to be a manifestation of spastic esophageal motility. Although future study to further clarify the significance of RRCs is needed, RRCs on FLIP panometry should prompt evaluation for a major motor disorder. NEW & NOTEWORTHY Repetitive retrograde contractions (RRCs) are a common response to sustained esophageal distension among spastic achalasia patients when evaluated with the functional luminal imaging probe. We evaluated patients with postfundoplication dysphagia, i.e., patients with suspected mechanical obstruction, and found that RRCs occasionally occurred among postfundoplication patients, but often in association with manometric features of esophageal neuromuscular imbalance. Thus, RRCs appear to be a manifestation of spastic esophageal dysmotility, likely from neural imbalance resulting in excess excitation.

The purpose of this review is to describe a place for per-oral endoscopic myotomy (POEM) among the currently available robust treatments for achalasia. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: 1) in determining the need for achalasia therapy, patient-specific parameters (Chicago Classification subtype, comorbidities, early vs late disease, primary or secondary causes) should be considered along with published efficacy data; 2) given the complexity of this procedure, POEM should be performed by experienced physicians in high-volume centers because an estimated 20−40 procedures are needed to achieve competence; 3) if the expertise is available, POEM should be considered as primary therapy for type III achalasia; 4) if the expertise is available, POEM should be considered as treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes; and 5) post-POEM patients should be considered high risk to develop reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy) of this before undergoing the procedure.

High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular achalasia. It has become apparent that the cardinal feature of achalasia — impaired lower oesophageal sphincter (LES) relaxation — can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting achalasia criteria that also benefit from therapies formerly reserved for achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of achalasia and achalasia-like syndromes.

Recent data suggest that effective control of gastroesophageal reflux improves outcomes associated with endoscopic eradication therapy (EET) for Barrett's esophagus (BE). However, the impact of reflux control on preventing recurrent intestinal metaplasia and/or dysplasia is unclear. The aims of the study were: (a) to determine the effectiveness and durability of EET under a structured reflux management protocol and (b) to determine the impact of optimizing anti-reflux therapy on achieving complete eradication of intestinal metaplasia (CE-IM).Consecutive BE patients referred for EET were enrolled and managed with a standardized reflux management protocol including twice-daily PPI therapy during eradication. Primary outcomes were rates of CE-IM and IM or dysplasia recurrence.Out of 221 patients enrolled (46.0% with high-grade dysplasia/intramucosal carcinoma, 34.0% with low-grade dysplasia, and 20.0% with non-dysplastic BE) an overall CE-IM of 93% was achieved within 11.6±10.2 months. Forty-eight patients did not achieve CE-IM in 3 sessions. After modification of their reflux management, 45 (93.7%) achieved CE-IM in a mean of 1.1 RFA sessions. Recurrence occurred in 13 patients (IM in 10(4.8%), dysplasia in 3 (1.5%)) during a mean follow-up of 44±18.5 months. The only significant predictor of recurrence was the presence of a hiatal hernia. Recurrence of IM was significantly lower than historical controls (10.9 vs. 4.8%, P=0.04).The current study highlights the importance of reflux control in patients with BE undergoing EET. In this setting, EET has long-term durability with low recurrence rates providing early evidence for extending endoscopic surveillance intervals after EET.

We aimed to evaluate the value of novel high-resolution impedance manometry (HRIM) metrics, bolus flow time (BFT), and esophagogastric junction (EGJ) contractile integral (CI), as well as EGJ pressure (EGJP) and the integrated relaxation pressure (IRP), as indicators of treatment response in achalasia.We prospectively evaluated 75 patients (ages 19-81, 32 female) with achalasia during follow-up after pneumatic dilation or myotomy with Eckardt score (ES), timed-barium esophagram (TBE), and HRIM. Receiver-operating characteristic (ROC) curves for good symptomatic outcome (ES≤3) and good radiographic outcome (TBE column height at 5 min5 cm) were generated for each potential predictor of treatment response (EGJP, IRP, BFT, and EGJ-CI).Follow-up occurred at a median (range) 12 (3-291) months following treatment. A total of 49 patients had good symptomatic outcome and 46 had good radiographic outcome. The area-under-the-curves (AUCs) on the ROC curve for symptomatic outcome were 0.55 (EGJP), 0.62 (IRP), 0.77 (BFT) and 0.56 (EGJ-CI). The AUCs for radiographic outcome were 0.64 (EGJP), 0.48 (IRP), 0.73 (BFT), and 0.65 (EGJ-CI). Optimal cut-points were determined as 11 mm Hg (EGJP), 12 mm Hg (IRP), 0 s (BFT), and 30 mm Hg•cm (EGJ-CI) that provided sensitivities/specificities of 57%/46% (EGJP), 65%/58% (IRP), 78%/77% (BFT), and 53%/62% (EGJ-CI) to predict symptomatic outcome and 57%/66% (EGJP), 57%/41% (IRP), 76%/69% (BFT), and 57%/66% (EGJ-CI) to predict radiographic outcome.BFT, a novel HRIM metric, provided an improved functional assessment over manometric measures of EGJP, IRP, and EGJ-CI at follow-up after achalasia treatment and may help direct clinical management.

Often 2-3 graduated pneumatic dilatations (PD) are required to treat achalasia as there is no current intra-procedural predictor of clinical response. Distensibility measurements using functional lumen imaging probe (FLIP) may provide an intra-procedural predictor of outcome. Our aim was to determine the optimal criterion for esophagogastric junction (EGJ) distensibility measurements during PD that predicts immediate clinical response.EGJ distensibility was prospectively measured using FLIP immediately pre- and post-PD. The EGJ distensibility index (EGJ-DI) was defined as a ratio of the narrowest cross-sectional area and the corresponding intra-bag pressure at 40 ml distension. Immediate and short-term clinical responses were defined as Eckardt score ≤3 assessed 2 weeks Post-PD and at 3-month follow-up, respectively.In 54 patients, we performed thirty-seven 30 mm; twenty 35 mm and six 40 mm PDs. The short-term response rate to the graded PD was 93% (27/29) in newly diagnosed achalasia; 87% (13/15) and 70% (7/10) in those who had relapsed after previous PD and Heller's Myotomy, respectively. Among those demonstrating an immediate response, EGJ-DI increased by an average of 4.5 mmFLIP-measured Δ EGJ-DI is a novel intra-procedural tool that accurately predicts immediate clinical response to PD in achalasia. This technique may potentially dictate an immediate mechanism to "step-up" dilator size within a single endoscopy session.

Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice. From a conventional pathophysiological perspective GERD is conceptualized as incompetence of the antireflux barrier at the esophagogastric junction; the more severe that incompetence, the worse the disease. However, it is increasingly clear that many presentations of GERD represent distinct phenotypes with unique predisposing cofactors and pathophysiology outside of this paradigm. Three major consensus initiatives have grappled with this dilemma (the Montreal Consensus, The Rome Foundation, and the Lyon Consensus), each from a different perspective. Montreal struggled to define the disease, Rome sought to characterize its “functional” attributes, while Lyon examined its physiological attributes. Our objective in this review is to merge the three, developing the concept that what has come to be known as GERD is actually a family of syndromes with a complex matrix of contributing pathophysiology. A corollary to this is that the concept of one size fits all to therapeutics does not apply and that while escalating treatment with proton pump inhibitors (PPIs) may be pertinent to healing esophagitis, its applicability beyond that is highly questionable. Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, visceral and central hypersensitivity on symptom severity has greatly over-simplified the problem. That over-simplification has led to excessive use of PPIs for everything captured under the GERD umbrella and revealed a broad spectrum of syndromes less amenable to PPI therapy in any dose. It is with this in mind that we delineate this precision medicine concept of GERD.

Background & Aims The etiologies of esophagogastric junction outflow obstruction (EGJOO) vary, as do their therapeutic implications. We aimed to identify patients with EGJOO most likely to benefit from achalasia-type treatment, based on findings from functional luminal imaging probe (FLIP) panometry. Methods We performed a retrospective study of 34 patients who received a diagnosis of EGJOO from January 2015 through July 2017. Our analysis included patients who had been evaluated with timed barium esophagram, FLIP, or upper endoscopy. Results Among the 34 patients with idiopathic EGJOO, 7 (21%) had a normal esophagogastric junction distensibility index (EGJ-DI), based on FLIP panometry, and all had repetitive antegrade contractions. None of the patients had radiographic evidence of EGJOO (RAD-EGJOO), defined as liquid barium retention and/or barium tablet impaction. On the other hand, all 18 patients with RAD-EGJOO had an EGJ-DI less than 2 mm2/mm Hg. Nine of the 18 patients with RAD-EGJOO and EGJ-DI less than 2 mm2/mm Hg underwent achalasia-type treatment, and 77.8% of these (7 of 9) had improvements in Eckardt score. Of the 6 patients with a normal EGJ-DI (>3 mm2/mm Hg) who were treated conservatively and followed up, 100% had improvements in subsequent Eckardt scores. Conclusions We found that FLIP is useful in identifying patients with EGJOO who are most likely to benefit from achalasia-type therapy. Patients with a low EGJ-DI responded well to achalasia-type treatment, whereas patients with normal results from FLIP panometry had good outcomes from conservative management. FLIP panometry might help select management strategies for this difficult population of patients.

Achalasia is a disorder of impaired lower esophageal sphincter (LES) relaxation and failed peristalsis traditionally characterized by manometry.1 As impaired LES relaxation is a mechanism of reduced esophagogastric junction (EGJ) opening, abnormally reduced EGJ distensibility assessed with functional luminal imaging probe (FLIP) was reported among patients with untreated achalasia.2-5 Therefore, we aimed to describe the performance characteristics of EGJ opening parameters on FLIP panometry among a large cohort of treatment-naive achalasia patients.

Gastroesophageal reflux disease (GERD) encompasses an array of disorders unified by the reflux of gastric contents. Because there are many potential disease manifestations, esophageal and extraesophageal, there is no single biomarker of the entire disease spectrum; a set of GERD biomarkers that each quantifies specific aspects of GERD-related pathology might be needed. We review recent reports of biomarkers of GERD, specifically in relation to endoscopically negative esophageal disease and excluding conventional pH-impedance monitoring. We consider histopathologic biomarkers, baseline impedance, and serologic assays to determine that most markers are based on manifestations of impaired esophageal mucosal integrity, which is based on increased ionic and molecular permeability, and/or destruction of tight junctions. Impaired mucosal integrity quantified by baseline mucosal impedance, proteolytic fragments of junctional proteins, or histopathologic features has emerged as a promising GERD biomarker.

Background & Aims The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Methods Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Results Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course.

Background & Aims Functional luminal imaging probe (FLIP) panometry provides a comprehensive evaluation of esophageal functional at the time of endoscopy, including assessment of esophageal distensibility and distension-induced esophageal contractility. However, the few and inconsistent findings from healthy individuals pose challenges to the application of FLIP to research and clinical practice. We performed FLIP panometry in asymptomatic volunteers. Methods We performed a prospective study of 20 asymptomatic volunteers (ages, 23–44; 14 women) who were evaluated with 16-cm FLIP positioned across the esophagogastric junction (EGJ) and distal esophagus (and in 8 subjects also repositioned at the proximal esophagus) during sedated upper endoscopy. FLIP data were analyzed with a customized program that generated FLIP panometry plots and calculated the EGJ-distensibility index (DI) and distensibility plateaus (DP) of distal and proximal esophageal body. Distension-induced esophageal contractility was also assessed. Results The median EGJ-DI was 5.8 mm2/mm Hg (interquartile range [IQR], 4.9–6.7 mm2/mm Hg); all 20 subjects had an EGJ-DI greater than 2.8 mm2/mm Hg. The median DP values from all subjects tested were 20.2 mm (IQR, 19.8–20.8 mm) at the distal body, 21.1 mm (IQR, 20.3–22.9 mm) at the proximal body, and greater than 18 mm at both locations. Repetitive antegrade contractions (RACs) were observed in all 20 subjects; in 19 of 20 (95%) subjects, the RAC pattern persisted for 10 or more consecutive antegrade contractions. Conclusions Normal parameters of FLIP panometry are EGJ-DI greater than 2.8 mm2/mm Hg, DP greater than 18 mm, and antegrade contractions that occur in a repetitive pattern (RACs)—these can be used as normal findings for esophageal distensibility and distension-induced contractility. These values can be used in comparative studies of esophageal diseases, such as achalasia and eosinophilic esophagitis, and will facilitate application of FLIP panometry to clinical practice.