A self-reinforcing regulatory network triggered by limiting IL-7 activates pre-BCR signaling and differentiation.

The molecular crosstalk between the interleukin 7 receptor (IL-7R) and the precursor to the B cell antigen receptor (pre-BCR) in B lymphopoiesis has not been elucidated. Here we demonstrate that in pre-B cells, the IL-7R but not the pre-BCR was coupled to phosphatidylinositol-3-OH kinase (PI(3)K) and the kinase Akt; signaling by this pathway inhibited expression of recombination-activating gene 1 (Rag1) and Rag2. Attenuation of IL-7 signaling resulted in upregulation of the transcription factors Foxo1 and Pax5, which coactivated many pre-B cell genes, including Rag1, Rag2 and Blnk. Induction of Blnk (which encodes the signaling adaptor BLNK) enabled pre-BCR signaling via the signaling molecule Syk and promoted immunoglobulin light-chain rearrangement. BLNK expression also antagonized Akt activation, thereby augmenting the accumulation of Foxo1 and Pax5. This self-reinforcing molecular circuit seemed to sense limiting concentrations of IL-7 and functioned to constrain the proliferation of pre-B cells and trigger their differentiation.

Development and initial validation of a video-based peroral endoscopic myotomy assessment tool.

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.

Esophageal Lichen Planus: A Descriptive Multicenter Report.

GOALS: To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP). BACKGROUND: ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series. STUDY: A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States. RESULTS: Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers. CONCLUSIONS: Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.

Paraesophageal hernia recurrence following repair: making the case for reoperative surgery in a propensity-matched cohort.

BACKGROUND: Paraesophageal hernia repairs (PEHRs) have high rates of radiographic recurrence, with some patients requiring repeat operation. This study characterizes patients who underwent PEHR to identify the factors associated with postoperative symptom improvement and radiographic recurrence. We furthermore use propensity score matching to compare patients undergoing initial and reoperative PEHR to identify the factors predictive of recurrence or need for reoperation. METHODS: After IRB approval, patients who underwent PEHR at a tertiary care center between January 2018 and December 2022 were identified. Patient characteristics, preoperative imaging, operative findings, and postoperative outcomes were recorded. A computational generalization of inverse propensity score weight was then used to construct populations of initial and redo PEHR patients with similar covariate distributions. RESULTS: A total of 244 patients underwent PEHR (78.7% female, mean age 65.4 ± 12.3 years). Most repairs were performed with crural closure (81.4%) and fundoplication (71.7%) with 14.2% utilizing mesh. Postoperatively, 76.5% of patients had subjective symptom improvement and of 157 patients with postoperative imaging, 52.9% had evidence of radiographic recurrence at a mean follow-up of 10.4 ± 13.6 months. Only 4.9% of patients required a redo operation. Hernia type, crural closure, fundoplication, and mesh usage were not predictors of radiographic recurrence or symptom improvement (P > 0.05). Propensity weight score analysis of 50 redo PEHRs compared to a matched cohort of 194 initial operations revealed lower rates of postoperative symptom improvement (P < 0.05) but no differences in need for revision, complication rates, ED visits, or readmissions. CONCLUSIONS: Most PEHR patients have symptomatic improvement with minimal complications and reoperations despite frequent radiographic recurrence. Hernia type, crural closure, fundoplication, and mesh usage were not significantly associated with recurrence or symptom improvement. Compared to initial PEHR, reoperative PEHRs had lower rates of symptom improvement but similar rates of recurrence, complications, and need for reoperation.

Outcomes in Enteral Access Based on Specialty and Approach: A Single-Center Three-Year Experience.

INTRODUCTION: Interventional radiologic, endoscopic, and surgical approaches are commonly utilized to establish durable enteral access in adult patients. The purpose of this study is to examine differences in nutritional outcomes in a large cohort of patients undergoing enteral access creation. METHODS: Adult patients who underwent enteral access procedures by interventional radiologists, gastroenterologists, and surgeons between 2018 and 2020 at a single institution were reviewed. Included access types were percutaneous endoscopic gastrostomy (PEG), open or laparoscopic gastrostomy, laparoscopic jejunostomy, and percutaneous gastrostomy (perc-G), percutaneous jejunostomy , or primary gastrojejunostomy. RESULTS: 912 patients undergoing enteral access cases met the criteria for inclusion. PEGs and perc-Gs were the most common procedures. PEGs had higher Charlson scores (4.5 [3.0-6.0] versus 2.0 [1.0-2.0], P = 0.007) and lower starting albumin (3.0 [2.6-3.4] versus 3.6 [3.5-3.8] g/dL, P < 0.0001). Time to goal feeds (4 [2-6] vs 4 [3-5] d, P = 0.970), delta prealbumin (3.6 [0-6.5] versus 6.2 [2.3-10] mg/L, P = 0.145), time to access removal (160 [60-220] versus 180 [90-300] d, P = 0.998), and enteral access-related complications (19% versus 16%, P = 0.21) between PEG and perc-G were similar and differences were not statistically significant. A greater percent change in prealbumin was noted for perc-G (10 [-3-20] versus 41.7% [11-65], P = 0.002). CONCLUSIONS: Despite having higher Charlson scores and worse preoperative nutrition, there is a similar incidence of enteral access-related complications, time to goal feeds, delta prealbumin, or time to access removal between PEG and perc-G patients. Our data suggest that access approach should be made on an individual basis, accounting for anatomy and technical feasibility.

Conversion to Roux-En-Y Gastric Bypass: a successful means of mitigating reflux after laparoscopic sleeve gastrectomy.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) has become the most common bariatric procedure due to the technical ease and weight loss success of the operation. However, there has been concern that LSG contributes to gastroesophageal reflux disease (GERD) postoperatively with a proportion of patients requiring conversion to a Roux-En-Y Gastric Bypass (RYGB). The objective of this study was to characterize the patients who underwent revision in our hospital system and to better understand pre-operative predictors of GERD and revision. METHODS: After IRB approval, a retrospective review was conducted assessing for patients who had conversion of LSG to RYGB at three hospitals within the University of Pennsylvania Health System from January 2015 to December 2021. The patients' charts were then reviewed to evaluate for demographics, BMI, operative findings, imaging and endoscopic reports, and post-operative outcomes. RESULTS: 97 patients were identified who underwent conversion of LSG to RYGB between January 2015 and December 2021. The cohort was predominantly female (n = 89, 91.7%) with an average age of 42.7 ± 10.6 years at the time of conversion. The most common indications for revision were GERD (72.2%) and obesity/insufficient weight loss (24.7%). Patients lost an average of 11.1 ± 12.9 kg after revision to RYGB. Of the patients who underwent revision for GERD, 80.2% noted global symptomatic improvement after revision and 19.4% were able to stop their proton pump inhibitor (PPI) postoperatively, with most patients decreasing the frequency of the PPI use postoperatively. CONCLUSION: The majority of patients who underwent conversion from LSG to RYGB due to GERD and saw marked improvements in GERD symptoms and outcomes. These findings illuminate the real-world practices and outcomes of bariatric revisional procedures for reflux and the need for more research on standardized practice.

Novel histologic score predicts recurrent intestinal metaplasia after successful endoscopic eradication therapy.

Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET <4% was 4.0 (1.6), compared with 5.5 (0.9) for AET ≥4% (P = 0.015). In the validation cohort consisting of 72 patients without recurrence and 64 patients with recurrence following EET, the RECUR score was the only significant predictor of recurrence (odds ratio: 1.36, 95% confidence interval: 1.10-1.69, P = 0.005). Histologic grading of surveillance biopsies using the RECUR scoring system correlates with BE recurrence following EET.

Gastric per-oral endoscopic myotomy (G-POEM) for refractory gastroparesis: results from an international prospective trial.

OBJECTIVE: Although gastric per-oral endoscopic myotomy (G-POEM) is considered a promising technique for the management of refractory gastroparesis, high-quality evidence is limited. We prospectively investigated the efficacy and safety of G-POEM in unselected patients with refractory gastroparesis. DESIGN: In five tertiary centres, patients with symptomatic gastroparesis refractory to standard medical therapy and confirmed by impaired gastric emptying were included. The primary endpoint was clinical success, defined as at least one score decrease in Gastroparesis Cardinal Symptom Index (GCSI) with ≥25% decrease in two subscales, at 12 months. GCSI Score and subscales, adverse events (AEs) and 36-Item Short Form questionnaire of quality of life were evaluated at baseline and 1, 3, 6 and 12 months after G-POEM. Gastric emptying study was performed before and 3 months after the procedure. RESULTS: Of 80 enrolled patients, 75 patients (94%) completed 12-month follow-up. Clinical success at 12 months was 56% (95% CI, 44.8 to 66.7). GCSI Score (including subscales) improved moderately after G-POEM (p<0.05). In a regression model, a baseline GCSI Score >2.6 (OR=3.23, p=0.04) and baseline gastric retention >20% at 4 hours (OR=3.65, p=0.03) were independent predictors of clinical success at 12 months, as was early response to G-POEM at 1 month after therapy (OR 8.75, p<0.001). Mild procedure-related AEs occurred in 5 (6%) patients. CONCLUSION: G-POEM is a safe procedure, but showed only modest overall effectiveness in the treatment of refractory gastroparesis. Further studies are required to identify the best candidates for G-POEM; unselective use of this procedure should be discouraged. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry NCT02732821.

Myotomy technique and esophageal contractility impact blown-out myotomy formation in achalasia: an in silico investigation.

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 Guides Proton Pump Inhibitor Discontinuation in Patients With Gastroesophageal Reflux Symptoms: A Clinical Trial.

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 < .001). Participants with 0 days of AET > 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).

Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy.

INTRODUCTION: 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. METHODS: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 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. RESULTS: 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). DISCUSSION: 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.

Can FLIP guide therapy in idiopathic esophagogastric junction outflow obstruction?

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) has a variable disease course. Currently, barium swallow (BaS) and manometric parameters are used to characterize clinically significant EGJOO. The esophagogastric junction distensibility index (EGJ-DI) measured via functional lumen imaging probe (FLIP) can provide complementary information. Our aim was to assess symptom response in patients with EGJOO and an abnormal EGJ-DI after botulinum toxin (BT) treatment. METHODS: A prospective cohort study of adults with idiopathic EGJOO was performed from September 2019 to March 2021. Patients with dysphagia underwent upper endoscopy with FLIP. If the EGJ-DI was abnormally low, BT was injected. Data examined included demographics, medical history, endoscopic and FLIP findings, BaS, manometry, and Eckardt score (ES). ES improvement was assessed via paired samples t-test. Pearson's chi-square tests were used to assess for associations. RESULTS: Of the 20 patients, 75% had an abnormal EGJ-DI and underwent BT injections. Mean ES for patients with abnormal EGJ-DIs significantly improved from baseline to 1, 3, and 6 month follow-up (P-values: 0.01, 0.05, and 0.02, respectively). There was a significant association between an abnormal EGJ-DI with delayed bolus transit and presence of rapid drink challenge panesophageal pressurization on manometry: P = 0.03 and P = 0.03. CONCLUSION: This prospective study revealed that an abnormal EGJ-DI can guide BT as assessed via symptomatic response. Additionally, abnormal EGJ-DI measurements were significantly associated with other parameters used previously to determine clinically relevant EGJOO. Larger follow-up studies are warranted to further elucidate guidance for therapy in EGJOO.

Outcomes of 100 Patients More Than 4 Years After POEM for Achalasia.

OBJECTIVE: We aim to describe the long-term follow-up data from our institution's POEM experience. SUMMARY BACKGROUND DATA: Per-oral endoscopic myotomy (POEM) is a well-established endoscopic therapy for achalasia with excellent short-term efficacy, but long-term outcomes data are limited. METHODS: Patients older than 4 years removed from POEM for treatment of achalasia were studied. Clinical success was defined as an Eckardt Symptom (ES) score ≤3 and freedom from reintervention for achalasia. Patients underwent esophagogastroduodenoscopy (EGD), high-resolution manometry, impedance planimetry, and timed barium esophagram (TBE) preoperatively and at least 4 years postoperatively. Objective gastroesophageal reflux disease (GERD) was defined LA Grade B or worse esophagitis on EGD. RESULTS: One hundred and nineteen consecutive patients were included. Five patients died or had catastrophic events unrelated to achalasia or POEM. One hundred of the remaining patients (88%, 100/114) had long-term data available. Clinical follow-up for all patients was greater than 4 years postoperatively and the mean was 55 months. Mean current ES was significantly improved from preop (n = 100, 1 ±â€Š1 vs 7 ±â€Š2, P < 0.001). Overall clinical success was 88% and 92%. Five patients had a current ES >3 and 4 patients required procedural reintervention on the lower esophageal sphincter. Reinterventions were successful in 75% of patients (3/4), with current ES ≤3. The rate of objective GERD was 33% (15/45). Esophageal physiology was improved with a decrease in median integrated relaxation pressure (11 ±â€Š4 vs 33 ±â€Š15 mm Hg, P < 0.001), a decrease in median TBE column height (3 ±â€Š3 vs 13 ±â€Š8 cm, P < 0.001), and an increase in median distensibility index (5.1 ±â€Š2 vs 1.1 ±â€Š1 mm2/mm Hg, P < 0.001). CONCLUSIONS: POEM provides durable symptom relief and improvement in physiologic esophagogastric junction relaxation parameters over 4.5 years postoperatively. Reinterventions are rare and effective.

Esophagogastric Junction Opening Parameters Are Consistently Abnormal in Untreated Achalasia.

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-naïve achalasia patients.

Normal Functional Luminal Imaging Probe Panometry Findings Associate With Lack of Major Esophageal Motility Disorder on High-Resolution Manometry.

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.

Blown-out myotomy: an adverse event of laparoscopic Heller myotomy and peroral endoscopic myotomy for achalasia.

BACKGROUND AND AIMS: Although laparoscopic Heller myotomy (LHM) or peroral endoscopic myotomy (POEM) is highly effective, 10% to 20% of patients with achalasia remain symptomatic after treatment. In evaluating such patients, we have observed a pattern of failure associated with a pseudodiverticulum, or blown-out myotomy (BOM), in the distal esophagus. We aimed to assess risk factors and patient-reported outcomes associated with a BOM. METHODS: We reviewed our manometry database for patients with achalasia previously treated with LHM or POEM. We included patients who had a post-treatment esophagram within 1 year of their follow-up manometry. A BOM was defined radiographically as a wide-mouthed outpouching (>50% increase in esophageal diameter) in the area of the myotomy. RESULTS: One hundred twenty-nine patients with achalasia who underwent treatment were included; 23 (17.8%) had a BOM. Comparing patients with a BOM with those without, post-treatment Eckardt scores were significantly greater (5 vs 2, P = .002), type III achalasia was more common (39.1% vs 14.2%, P = .005), and LHM was more common than POEM (73.9% vs 26.1%, P = .013). The integrated relaxation pressure was also significantly greater in the BOM group (15.0 mm Hg vs 11.0 mm Hg, P = .025). CONCLUSIONS: BOM is a common adverse event after myotomy for achalasia but is not seen after pneumatic dilation. Pretreatment type III achalasia, LHM as opposed to POEM, and a greater post-treatment integrated relaxation pressure were risk factors for developing a BOM. We speculate that esophageal wall strain in the area weakened by myotomy, whether from residual spastic contractility or continued esophageal outflow obstruction, may be the underlying mechanism of BOM development.

Type II achalasia is associated with a comparably favorable outcome following per oral endoscopic myotomy.

Per oral endoscopic myotomy (POEM) is a safe and effective treatment for esophageal motility disorder in treatment-naïve patients as well as salvage therapy. Though type II achalasia, compared to other subtypes, is reported to have a more favorable outcome with pneumatic dilation (PD) or Heller myotomy (HM), it is unclear whether achalasia subtype predicts symptom response to POEM. We aimed to evaluate whether type II achalasia is associated with a comparably favorable outcome following POEM. We performed a retrospective review of patients with esophageal motility disorder who were referred for POEM from April 2014 to June 2017. The main outcome was clinical success based on Eckardt score ≤3 and its association with subtype and safety. A total of 63 patients (mean age 51 years [SD 15]; 63% male) underwent a total of 68 POEMs with median of 263 days follow-up. Of these, 45 (71.3%) patients were type II achalasia. In all, 29 (46%) patients were treatment-naïve and 34 (54%) patients had previous endoscopic or surgical therapy including botulinum toxin injection in 16 (25%), PD in 10 (16%), both botulinum toxin injection and PD in 8 (13%) and HM in 3 (5%). Technical success was 100% and clinical success was achieved in 51 (81%) patients. The rate of clinical success was higher in patients with type II achalasia compared to the other subtypes (88.9% vs. 61.1% [P = 0.028]) and type II achalasia patients required fewer redo POEM (2.2% vs. 22.2% [P = 0.021]). Multivariate logistic regression analysis demonstrated the positive prediction of clinical success for type II achalasia following POEM (P = 0.046). As observed with PD and HM, type II achalasia was associated with a favorable clinical outcome following POEM.

Functional Luminal Imaging Probe Panometry Identifies Achalasia-Type Esophagogastric Junction Outflow Obstruction.

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.

Esophageal Hypervigilance and Visceral Anxiety Are Contributors to Symptom Severity Among Patients Evaluated With High-Resolution Esophageal Manometry.

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.

Treatment experience with a novel 30-mm hydrostatic balloon in esophageal dysmotility: a multicenter retrospective analysis.

BACKGROUND AND AIMS: The newest addition in the management of achalasia and esophagogastric junction outflow obstruction (EGJOO) is a 30-mm hydrostatic balloon dilator that uses impedance planimetry technology. It allows for the measurement of the diameter and cross-sectional area to determine effective dilation. We aimed to (1) determine the clinical success (defined as a decrease in Eckardt score to ≤3) in the treatment of esophageal motility disorders and (2) report the safety (rate/severity of adverse events). METHODS: This retrospective multicenter study involved 4 centers. Patients with esophageal motility disorders who underwent hydrostatic balloon dilation between January 2015 and October 2018 were included. RESULTS: Fifty-one patients (mean age, 54.1 years; women, 49%) underwent hydrostatic dilation for achalasia (n = 37) or EGJOO (n = 14) during the study period. Forty-seven patients had a median baseline Eckardt score of 5 (range, 3-8; achalasia, n = 35, 6 [range, 3-8]; EGJOO, n = 12, 4 [range, 3.25-6.5]). Clinical success was achieved in 60% of cases (achalasia vs EGJOO: 68.4% vs 33.3%, P = .18). Dilation resulted in a significant decrease in the median Eckardt score from 5 (range, 3-8) to 1.5 (range, 1-4.75; P < .001). Patients with achalasia had a decrease in Eckardt score from 6 (range, 3-8) to 1 (range, 1-4; P < .001), whereas those with EGJOO experienced no significant change. One patient had mild postprocedure chest pain. CONCLUSIONS: The hydrostatic balloon dilator is a new tool in our armamentarium to treat esophageal motility disorders. This is the first multicenter study showing the device to be safe and moderately efficacious.