Updates to the modern diagnosis of GERD: Lyon consensus 2.0.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

Comparison of drugs for active eosinophilic oesophagitis: systematic review and network meta-analysis.

BACKGROUND: There is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE. METHODS: We searched MEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials from inception to June 2023. We included randomised controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with active EoE. Results were reported as pooled relative risks with 95% CIs to summarise effect of each comparison tested, with drugs ranked according to P score RESULTS: Seventeen RCTs were eligible for systematic review. Of these, 15 studies containing 1813 subjects with EoE reported extractable data for the network meta-analysis. For histological remission defined as ≤6 eosinophils/high-power field (HPF), lirentelimab 1 mg/kg monthly ranked first. For histological remission defined as ≤15 eosinophils/HPF, budesonide orally disintegrating tablet (BOT) 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE Endoscopic Reference Score, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo. CONCLUSIONS: Although this network meta-analysis supports the efficacy of most available drugs over placebo for EoE treatment, significant heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy.

Rapid Drink Challenge During High-resolution Manometry for Evaluation of Esophageal Emptying in Treated Achalasia.

BACKGROUND & AIMS: Incomplete esophageal emptying is a key variable predicting symptom relapse after achalasia treatment. Although optimally evaluated using the timed barium esophagogram (TBE), incomplete esophageal emptying can also be identified on rapid drink challenge (RDC) performed during high-resolution manometry. METHODS: We evaluated if RDC differentiates complete from incomplete esophageal emptying in treated patients with achalasia, against a TBE gold standard. Unselected treated patients with achalasia with both TBE (200 mL of low-density barium suspension) and RDC (200 mL of water in sitting position) were enrolled in 5 tertiary referral centers. TBE barium column height at 1, 2, and 5 minutes were compared with RDC variables: pressurizations >20 mmHg, maximal RDC pressurization, proportion of RDC time occupied by pressurizations, trans-esophagogastric junction gradient, and integrated relaxation pressure. RESULTS: Of 175 patients recruited (mean age, 59 years; 47% female), 138 (79%) were in clinical remission. Complete TBE emptying occurred in 45.1% at 1 minute, 64.0% at 2 minutes, and 73.1% at 5 minutes. RDC integrated relaxation pressure correlated strongly with TBE column height, and a 10-mmHg threshold discriminated complete from incomplete emptying at all 3 TBE time points with area under receiver operating characteristic curves of 0.85, 0.87, and 0.85, respectively. This threshold had high negative predictive values for complete emptying (88% at 2 minutes, 94% at 5 minutes), and modest positive predictive values for incomplete emptying (77% at 2 minutes, 62% at 5 minutes). CONCLUSIONS: RDC during high-resolution manometry is an effective surrogate for TBE in assessing esophageal emptying in treated patients with achalasia.

Improving the Diagnostic Yield of High-Resolution Esophageal Manometry for GERD: The "Straight Leg-Raise" International Study.

BACKGROUND & AIMS: The straight leg raise (SLR) maneuver during high-resolution manometry (HRM) can assess esophagogastric junction (EGJ) barrier function by measuring changes in intraesophageal pressure (IEP) when intra-abdominal pressure is increased. We aimed to determine whether increased esophageal pressure during SLR predicts pathologic esophageal acid exposure time (AET). METHODS: Adult patients with persistent gastroesophageal reflux disease (GERD) symptoms undergoing HRM and pH-impedance or wireless pH study off proton pump inhibitor were prospectively studied between July 2021 and March 2022. After the HRM Chicago 4.0 protocol, patients were requested to elevate 1 leg at 45º for 5 seconds while supine. The SLR maneuver was considered effective when intra-abdominal pressure increased by 50%. IEPs were recorded 5 cm above the lower esophageal sphincter at baseline and during SLR. GERD was defined as AET greater than 6%. RESULTS: The SLR was effective in 295 patients (81%), 115 (39%) of whom had an AET greater than 6%. Hiatal hernia (EGJ type 2 or 3) was seen in 135 (46%) patients. Compared with patients with an AET less than 6%, peak IEP during SLR was significantly higher in the GERD group (29.7 vs 13.9 mm Hg; P < .001). Using receiver operating characteristic analysis, an increase of 11 mm Hg of peak IEP from baseline during SLR was the optimal cut-off value to predict an AET greater than 6% (area under the receiver operating characteristic curve, 0.84; sensitivity, 79%; and specificity, 85%), regardless of the presence of hiatal hernia. On multivariable analysis, an IEP pressure increase during the SLR maneuver, EGJ contractile integral, EGJ subtype 2, and EGJ subtype 3, were found to be significant predictors of AET greater than 6% CONCLUSIONS: The SLR maneuver can predict abnormal an AET, thereby increasing the diagnostic value of HRM when GERD is suspected. CLINICALTRIALS: gov ID: NCT04813029.

Six-Food Elimination Diet Is Less Effective During Pollen Season in Adults With Eosinophilic Esophagitis Sensitized to Pollens.

INTRODUCTION: The role of inhaled and swallowed aeroallergens in treatment outcomes of adult patients with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of the 6-food elimination diet (SFED) in EoE. METHODS: We compared outcomes of patients with EoE who underwent SFED during vs outside of the pollen season. Consecutive adult patients with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Individual pollen sensitization and pollen count data were analyzed to define whether each patient had been assessed during or outside of the pollen season after SFED. All patients had active EoE (≥15 eosinophils/high-power field) before SFED and adhered to the diet under the supervision of a dietitian. RESULTS: Fifty-eight patients were included, 62.0% had positive SPT for birch and/or grass, whereas 37.9% had negative SPT. Overall, SFED response was 56.9% (95% confidence interval, 44.1%-68.8%). When stratifying response according to whether the assessment had been performed during or outside of the pollen season, patients sensitized to pollens showed significantly lower response to SFED during compared with outside of the pollen season (21.4% vs 77.3%; P = 0.003). In addition, during the pollen season, patients with pollen sensitization had significantly lower response to SFED compared with those without sensitization (21.4% vs 77.8%; P = 0.01). DISCUSSION: Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. The SPT for pollens may identify patients less likely to respond to the diet during the pollen season.

Ambulatory pH-Impedance Findings Confirm That Grade B Esophagitis Provides Objective Diagnosis of Gastroesophageal Reflux Disease.

INTRODUCTION: The Lyon Consensus designates Los Angeles (LA) grade C/D esophagitis or acid exposure time (AET) >6% on impedance-pH monitoring (MII-pH) as conclusive for gastroesophageal reflux disease (GERD). We aimed to evaluate proportions with objective GERD among symptomatic patients with LA grade A, B, and C esophagitis on endoscopy. METHODS: Demographics, clinical data, endoscopy findings, and objective proton-pump inhibitor response were collected from symptomatic prospectively enrolled patients from 2 referral centers. Off-therapy MII-pH parameters included AET, number of reflux episodes, mean nocturnal baseline impedance, and postreflux swallow-induced peristaltic wave index. Objective GERD evidence was compared between LA grades. RESULTS: Of 155 patients (LA grade A: 74 patients, B: 61 patients, and C: 20 patients), demographics and presentation were similar across LA grades. AET >6% was seen in 1.4%, 52.5%, and 75%, respectively, in LA grades A, B, and C. Using additional MII-pH metrics, an additional 16.2% with LA grade A and 47.5% with LA grade B esophagitis had AET 4%-6% with low mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index; there were no additional gains using the number of reflux episodes or symptom-reflux association metrics. Compared with LA grade C (100% conclusive GERD based on endoscopic findings), 100% of LA grade B esophagitis also had objective GERD but only 17.6% with LA grade A esophagitis ( P < 0.001 compared with each). Proton-pump inhibitor response was comparable between LA grades B and C (74% and 70%, respectively) but low in LA grade A (39%, P < 0.001). DISCUSSION: Grade B esophagitis indicates an objective diagnosis of GERD.

Endoluminal Procedures and Devices for Esophageal Tract Investigation: A Critical Review.

Diseases of the esophageal tract represent a heterogeneous class of pathological conditions for which diagnostic paradigms continue to emerge. In the last few decades, innovative diagnostic devices have been developed, and several attempts have been made to advance and standardize diagnostic algorithms to be compliant with medical procedures. To the best of our knowledge, a comprehensive review of the procedures and available technologies to investigate the esophageal tract was missing in the literature. Therefore, the proposed review aims to provide a comprehensive analysis of available endoluminal technologies and procedures to investigate esophagus health conditions. The proposed systematic review was performed using PubMed, Scopus, and Web of Science databases. Studies have been divided into categories based on the type of evaluation and measurement that the investigated technology provides. In detail, three main categories have been identified, i.e., endoluminal technologies for the (i) morphological, (ii) bio-mechanical, and (iii) electro-chemical evaluation of the esophagus.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

Current and Novel Therapies for Eosinophilic Gastrointestinal Diseases.

Eosinophilic gastrointestinal diseases (EGIDs) are an emerging group of pathological entities characterized by an eosinophil-predominant infiltration of different tracts of the gut in the absence of secondary causes of eosinophilia. According to the specific tract of the gut involved, EGIDs can be classified into eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The epidemiology of EGIDs is evolving rapidly. EoE, once considered a rare disease, now has an incidence and prevalence of 7.7 new cases per 100,000 inhabitants per years and 34.4 cases per 100,000 inhabitants per year, respectively. Fewer data are available regarding non-EoE EGIDs, whose prevalence are estimated to range between 2.1 and 17.6 in 100,000 individuals, depending on age, sex, and ethnicity. Diagnosis requires the presence of suggestive symptoms, endoscopic biopsies showing abnormal values of eosinophils infiltrating the gut, and exclusion of secondary causes of eosinophilia. EoE typically presents with dysphagia and episodes of food bolus impactions, while EoG, EoN, and EoC may all present with abdominal pain and diarrhea, with or without other non-specific symptoms. In addition, although different EGIDs are currently classified as different entities, there may be overlap between different diseases in the same patient. Despite EGIDs being relatively novel pathological entities, the research on possible treatments is rapidly growing. In this regard, several randomized controlled trials are currently ongoing to investigate novel molecules, including ad-hoc steroid formulations, immunosuppressants, and mostly monoclonal antibodies that target the specific molecular mediators of EGIDs. This narrative review provides an up-to-date overview of available and investigational drugs for different EGIDs.

Esophageal dysmotility in patients with eosinophilic esophagitis: pathogenesis, assessment tools, manometric characteristics, and clinical implications.

Eosinophilic esophagitis (EoE) represents a growing cause of chronic esophageal morbidity whose incidence and prevalence are increasing rapidly. The disease is characterized by eosinophilic infiltrates of the esophagus and organ dysfunction. Typical symptoms include dysphagia, chest pain, and bolus impaction, which are associated to mechanical obstructions in most patients. However, up to one in three EoE patients has no visible obstruction, suggesting that a motor disorder of the esophagus may underlie symptoms. Although potentially relevant for treatment refractoriness and symptomatic burden, esophageal dysmotility is often neglected when assessing EoE patients. The first systematic review investigating esophageal motility patterns in patients with EoE was published only recently. Accordingly, we reviewed the pathogenesis, assessment tools, manometric characteristics, and clinical implications of dysmotility in patients with EoE to highlight its clinical relevance. In summary, eosinophils can influence the amplitude of esophageal contractions via different mechanisms. The prevalence of dysmotility may increase with disease duration, possibly representing a late feature of EoE. Patients with EoE may display a wide range of motility disorders and possible disease-specific manometric pressurization patterns may be useful for raising a clinical suspicion. Intermittent dysmotility events have been found to correlate with symptoms on prolonged esophageal manometry, although high-resolution manometry studies have reported inconsistent results, possibly due to the suboptimal sensitivity of current manometry protocols. Motor abnormalities may recover following EoE treatment in a subset of patients, but invasive management of the motor disorder is required in some instances. In conclusion, esophageal motor abnormalities may have a role in eliciting symptoms, raising clinical suspicion, and influencing treatment outcome in EoE. The assessment of esophageal motility appears valuable in the EoE setting.

Application of Lyon Consensus criteria for GORD diagnosis: evaluation of conventional and new impedance-pH parameters.

OBJECTIVE: To validate Lyon Consensus criteria for diagnosing gastro-oesophageal reflux disease (GORD) by reflux monitoring. DESIGN: Manual review of impedance-pH tracings from patients with proton pump inhibitor (PPI)-dependent heartburn, evaluated off PPI. Acid exposure time (AET) thresholds defined by the Lyon Consensus and impedance parameters were investigated, namely, total refluxes (TRs), postreflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI). RESULTS: The study included 488 patients, 178 (36%) with normal (<4%) AET, 89 (18%) with inconclusive (4%-6%) AET and 221 (45%) with abnormal (>6%) AET, alongside with 70 healthy controls. At receiver operating characteristic analysis, area under curve was 0.89, 0.95 and 0.89 for TRs, PSPW index and MNBI, respectively, and threshold values were 40, 50% and 2000 Ω; the 4% physiological AET threshold defined by the Lyon Consensus showed 100% specificity but 63% sensitivity. The thresholds defined for impedance parameters were validated against AET by means of ordered logistic regression, being in concordance with the 4% AET threshold (OR 2.5 for TRs, 18.9 for PSPW index and 5.7 for MNBI). TRs positivity and concordant PSPW index/MNBI positivity were found in 80%-90% of patients in the abnormal AET group, in 73%-74% of cases in the inconclusive AET group and in 28%-40% of cases in the group with normal AET. CONCLUSIONS: Our results show the overall validity of the Lyon Consensus approach to GORD diagnosis. Adding evaluation of impedance parameters, namely, TRs, PSPW index and MNBI to AET appraisal, substantially improves the diagnostic yield of reflux monitoring.

Value of pH Impedance Monitoring While on Twice-Daily Proton Pump Inhibitor Therapy to Identify Need for Escalation of Reflux Management.

BACKGROUND AND AIMS: Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH impedance studies performed while on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from "on PPI" pH impedance studies predicting need for escalation of therapy. METHODS: De-identified pH impedance studies performed while on twice-daily PPI (Diversatek, Boulder, CO) in healthy volunteers (n = 66, median age 37.5 years, 43.9% female), and patients with proven gastroesophageal reflux disease (GERD) (European heartburn-predominant cohort: n = 43, median age 57.0 years, 55.8% female; North American regurgitation-predominant cohort: n = 42, median age 41.6 years, 42.9% female) were analyzed. Median values and interquartile ranges for pH impedance metrics in healthy volunteers were compared with proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response. RESULTS: Both conventional and novel reflux metrics were similar between PPI responders and nonresponders (P ≥ .1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P = .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P = .002); 79% with these metrics improved with invasive GERD management. CONCLUSION: Combinations of abnormal "on PPI" pH impedance metrics are associated with PPI nonresponse in proven GERD patients, and can be targeted for treatment escalation, including surgery, particularly in regurgitation-predominant GERD.

Efficacy of a Second PPI Course After Steroid-Induced Remission in Eosinophilic Esophagitis Refractory to Initial PPI Therapy.

INTRODUCTION: Eosinophilic esophagitis (EoE) requires maintenance therapy to avoid recurrence. We investigated the efficacy of a second course of proton pump inhibitors (scPPIs) to maintain steroid-induced histological remission (HR) in patients with EoE who had previously failed induction of remission with PPIs. METHODS: We retrospectively included 18 patients who achieved HR with topical steroids but could not be maintained on long-term topical steroids. Treatment outcomes were assessed after 12 weeks of scPPIs. RESULTS: Most of the patients (67%) maintained HR with high-dose PPI monotherapy at week 12. DISCUSSION: scPPIs might work as a maintenance strategy in primary PPI nonresponder EoE patients.

Artificial Intelligence in the Diagnosis of Upper Gastrointestinal Diseases.

Artificial intelligence (AI) has enormous potential to support clinical routine workflows and therefore is gaining increasing popularity among medical professionals. In the field of gastroenterology, investigations on AI and computer-aided diagnosis (CAD) systems have mainly focused on the lower gastrointestinal (GI) tract. However, numerous CAD tools have been tested also in upper GI disorders showing encouraging results. The main application of AI in the upper GI tract is endoscopy; however, the need to analyze increasing loads of numerical and categorical data in short times has pushed researchers to investigate applications of AI systems in other upper GI settings, including gastroesophageal reflux disease, eosinophilic esophagitis, and motility disorders. AI and CAD systems will be increasingly incorporated into daily clinical practice in the coming years, thus at least basic notions will be soon required among physicians. For noninsiders, the working principles and potential of AI may be as fascinating as obscure. Accordingly, we reviewed systematic reviews, meta-analyses, randomized controlled trials, and original research articles regarding the performance of AI in the diagnosis of both malignant and benign esophageal and gastric diseases, also discussing essential characteristics of AI.

Clinical use of mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index for the diagnosis of gastro-esophageal reflux disease.

The clinical diagnosis of gastro-esophageal reflux disease (GERD) is based on the presence of typical esophageal troublesome symptoms. In clinical practice, heartburn relief following a proton pump inhibitor (PPI) trial or endoscopy can confirm a diagnosis of GERD. In cases of diagnostic uncertainty or before anti-reflux interventions, combined impedance-pH monitoring (MII-pH) provides a comprehensive assessment of both physical and chemical properties of the refluxate, allowing to achieve a conclusive diagnosis of GERD. Recently, the Lyon Consensus proposed the use of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW-I) as novel MII-pH metrics to support the diagnosis of GERD. The calculation of MNBI and PSPW-I currently needs to be performed manually, but artificial intelligence systems for the automated analysis of MII-pH tracings are being developed. Several studies demonstrated the increased diagnostic yield MNBI and PSPW-I for the categorization of patients with GERD at both on- and off-PPI MII-pH monitoring. Accordingly, we performed a narrative review on the clinical use and diagnostic yield of MNBI and PSPW-I when the diagnosis of GERD is uncertain. Based on currently available evidence, we strongly support the evaluation of PSPW-I and MNBI as part of the standard assessment of MII-pH tracings for the evaluation of GERD, especially in patients with endoscopy-negative heartburn.

Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients With Eosinophilic Esophagitis.

BACKGROUND: An association has been reported between achalasia and eosinophilic esophagitis (EoE). We performed a retrospective study of high-resolution manometry (HRM) patterns in a large cohort of patients with EoE. MATERIAL AND METHODS: We collected data from consecutive patients with a new diagnosis of EoE from 2012 through 2019 undergoing HRM during the initial assessment at different centers in Italy. Demographic, clinical, endoscopic and histological characteristics were recorded at baseline and during management. Diagnoses of EoE and esophageal motility disorders were made according to established criteria. Treatments offered included proton pump inhibitors and topical steroids for EoE, and pneumatic dilation and myotomy for achalasia. Response to therapy was defined as less than 15 eosinophils per high power field in esophageal biopsies. RESULTS: Of 109 consecutive patients (mean age 37 years, 82 male), 68 (62%) had normal findings from HRM. Among 41 patients with motor disorders, 24 (59%) had minor motor disorders and 17 (41%) presented with major motor disorders, including 8 with achalasia (1 with type 1, 4 with type 2, and 3 with type 3). Achalasia and nonachalasia obstructive motor disorders had 14.7% prevalence among patients with EoE. Achalasia was more frequent in women, with longer diagnostic delay and abnormal esophagogram (P < .05) compared with EoE without achalasia or obstructive motor disorders. Clinical features and endoscopic findings did not differ significantly between patients with EoE with vs without achalasia and obstructive motor disorders. A higher proportion of patients without achalasia and obstructive motor disorders responded to topical steroids than patients with these features (P < .005). Invasive achalasia management was required for symptom relief in 50% of patients with achalasia and obstructive motor disorders. CONCLUSION: Achalasia and obstructive motor disorders are found in almost 15% of patients with EoE, and esophageal eosinophilia might cause these disorders. Patients with EoE who do not respond to standard treatments might require targeted muscle disruption.

Hypercontractile Esophagus From Pathophysiology to Management: Proceedings of the Pisa Symposium.

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.

Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world.

OBJECTIVE: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. DESIGN: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). RESULTS: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. CONCLUSION: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings.

Assessment of serum cytokines predicts clinical and endoscopic outcomes to vedolizumab in ulcerative colitis patients.

AIMS: Vedolizumab (VDZ) prevents migration of activated leucocytes into inflamed mucosa. This study aimed to assess the patterns of serum cytokines in ulcerative colitis (UC) patients at baseline and during VDZ treatment, and to investigate their association with mucosal healing and clinical remission. METHODS: We enrolled consecutive UC patients eligible for treatment with VDZ. A panel of serum cytokines were measured by fluorescence assay at weeks 0, 6 and 22. Colonoscopy was performed at baseline and week 54, to evaluate mucosal healing. The time trends of serum cytokines were analysed by log-linear mixed effect models, and their prognostic accuracy was evaluated by logistic regression. RESULTS: Out of 27 patients included in the analysis, at week 54 mucosal healing was achieved in 12 (44%) and clinical remission in 17 (63%). Mucosal healing was associated with higher interleukin (IL)-8 values at baseline and with significant decrease in IL-6 and IL-8 levels over the first 6 weeks. A significant reduction of IL-6 and IL-8 levels over the first 6 weeks of treatment was associated also with clinical remission. Logistic models including, among the predictors, IL-6 and IL-8 at baseline and their changes over the first 6 weeks of treatment had 83% sensitivity and 87% specificity to predict mucosal healing, and 82% sensitivity and 90% specificity to predict clinical remission. CONCLUSION: In UC patients, the serum patterns of IL-6 and IL-8 at baseline and over the first 6 weeks of treatment with VDZ could be useful to predict therapeutic outcome.

Corticosteroid Treatment at Diagnosis: An Analysis of Relapses, Disease Extension, and Colectomy Rate in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis is a chronic relapsing disease usually treated with mesalamine. The need of steroid therapy at diagnosis is generally considered as a poor prognostic factor. AIMS: The aim of our study was to assess whether patients treated with corticosteroids at diagnosis have more clinical relapses, disease progression, or an increased risk of colectomy during a 5-year follow-up. METHODS: We retrospectively evaluated patients who had received diagnosis of ulcerative colitis with a 5-year follow-up. Relapse was defined as a worsening of symptoms requiring an increase in medical treatment. Progression of disease was defined as a proximal extension of mucosal involvement, comparing the colonoscopy performed 5 years after diagnosis with the first one. The need of corticosteroid treatment at diagnosis was correlated to number of relapses, disease progression, and colectomy rate. RESULTS: We included 230 patients, 116 of them (50%) treated with steroids at diagnosis. Multivariate analysis demonstrated that there is a strong correlation between corticosteroid use and number of relapses (p < 0.01), as well as with disease progression (p < 0.05). Seventeen patients (7.4%) underwent colectomy, but the correlation with steroids was not statistically significant. CONCLUSIONS: These data provide evidence that the need of corticosteroids at diagnosis is associated with a worse clinical outcome.