Functional lumen imaging probe topography identifies patients with normal acid exposure and esophageal hypervigilance amongst proton-pump inhibitor non-responders.

BACKGROUND: Multiple factors contribute to symptom generation and treatment response in proton-pump inhibitor non-responders (PPI-NRs). We aimed to test whether PPI-NRs with normal acid exposure have a higher degree of esophageal hypersensitivity and hypervigilance and can be identified using functional lumen imaging probe (FLIP) topography at the time of endoscopy. METHODS: Data from PPI-NRs whom underwent endoscopy, FLIP and wireless 96-h pH-metry were retrospectively analyzed. Patients were grouped according to acid exposure time (AET) as (a) 0 days abnormal (AET > 6%), (b) 1-2 days abnormal, or (c) 3-4 days abnormal. The esophageal hypervigilance and anxiety scale (EHAS) score and other symptom scores were compared between groups. The discriminatory ability of the esophagogastric junction (EGJ) distensibility index (DI) and max EGJ diameter in identifying patients with 0 days abnormal AET was tested via receiver-operating-characteristic (ROC) curve analysis. RESULTS: EHAS score was 38.6 in the 0 days abnormal AET group, 30.4 in the 1-2 days abnormal AET group (p = 0.073 when compared to 0 days abnormal) and 28.2 in the 3-4 days abnormal AET group (p = 0.031 when compared to 0 days abnormal). Area-under-the-curve (AUC) for the DI in association with 0 days AET > 6% was 0.629. A DI of < 2.8 mm2/mmHg had a sensitivity of 83.3%, and negative predictive value of 88% in classifying patients with 0 days abnormal acid exposure (p = 0.004). CONCLUSIONS: FLIP complements prolonged wireless pH-metry in distinguishing the subset of PPI-NRs with completely normal acid exposure and a higher burden of esophageal hypervigilance. Proper identification of patients along the functional heartburn spectrum can improve overall surgical outcomes.

Interrater Reliability of Functional Lumen Imaging Probe Panometry and High-Resolution Manometry for the Assessment of Esophageal Motility Disorders.

INTRODUCTION: High-resolution manometry (HRM) and functional lumen imaging probe (FLIP) are primary and/or complementary diagnostic tools for the evaluation of esophageal motility. We aimed to assess the interrater agreement and accuracy of HRM and FLIP interpretations. METHODS: Esophageal motility specialists from multiple institutions completed the interpretation of 40 consecutive HRM and 40 FLIP studies. Interrater agreement was assessed using intraclass correlation coefficient (ICC) for continuous variables and Fleiss' κ statistics for nominal variables. Accuracies of rater interpretation were assessed using the consensus of 3 experienced raters as the reference standard. RESULTS: Fifteen raters completed the HRM and FLIP studies. An excellent interrater agreement was seen in supine median integral relaxation pressure (ICC 0.96, 95% confidence interval 0.95-0.98), and a good agreement was seen with the assessment of esophagogastric junction (EGJ) outflow, peristalsis, and assignment of a Chicago Classification version 4.0 diagnosis using HRM (κ = 0.71, 0.75, and 0.70, respectively). An excellent interrater agreement for EGJ distensibility index and maximum diameter (0.91 [0.90-0.94], 0.92 [0.89-0.95]) was seen, and a moderate-to-good agreement was seen in the assignment of EGJ opening classification, contractile response pattern, and motility classification (κ = 0.68, 0.56, and 0.59, respectively) on FLIP. Rater accuracy for Chicago Classification version 4.0 diagnosis on HRM was 82% (95% confidence interval 78%-84%) and for motility diagnosis on FLIP Panometry was 78% (95% confidence interval 72%-81%). DISCUSSION: Our study demonstrates high levels of interrater agreement and accuracy in the interpretation of HRM and FLIP metrics and moderate-to-high levels for motility classification in FLIP, supporting the use of these approaches for primary or complementary evaluation of esophageal motility disorders.

Expanding the role of pneumatic dilation for nonachalasia patients: a comparative study.

BACKGROUND AND AIMS: Treatment options for nonachalasia obstructive disorders of the esophagogastric junction (EGJ) are limited. The aim of this study was to assess the treatment efficacy of pneumatic dilation (PD) for the disorders of EGJ outflow obstruction (EGJOO) and postfundoplication EGJ obstruction (PF-EGJO) and to assess attitudes regarding training in PD. METHODS: This was a 2-part study. The main study was a prospective, single-center study comparing treatment outcomes after PD in patients with EGJOO and PF-EGJO, defined using manometry criteria, versus achalasia. Treatment success was defined as a post-PD Eckardt score (ES) of ≤2 at the longest duration of follow-up available. In a substudy, a 2-question survey was sent to 78 advanced endoscopy fellowship sites in the United States regarding training in PD. RESULTS: Of the 58% of respondents to the advanced endoscopy program director survey, two-thirds reported no training in PD at their program. The primary rationale cited was lack of a clinical need for PD. Sixty-one patients (15 achalasia, 32 EGJOO, and 14 PF-EGJO) were included in the main study with outcomes available at a mean follow-up of 8.8 months. Overall, mean ES decreased from 6.30 to 2.89 (P < .0001), and a mean percentage of improvement in symptoms reported by patients was 55.3%. ES ≤2 was achieved by 33 of 61 patients (54.1%). CONCLUSIONS: PD is an effective treatment for the nonachalasia obstructive disorders of the EGJ. There may be a current gap in training and technical expertise in PD.

Classifying Esophageal Motility by FLIP Panometry: A Study of 722 Subjects With Manometry.

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

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.

Utilizing functional lumen imaging probe in directing treatment for post-fundoplication dysphagia.

BACKGROUND: Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia. METHODS: We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist's description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI) < 2.8 mm2/mmHg on real-time FLIP. In patients with EGJO and dysphagia, EGJ dilation was performed to 20 mm, 30 mm, or 35 mm in a stepwise fashion. Outcome was assessed as % dysphagia improvement during phone call or on brief esophageal dysphagia questionnaire (BEDQ) score. RESULTS: Twenty-six patients were included, of whom 17 (65%) had a low EGJ-DI. No patients had a hiatal hernia greater than 3 cm. Dysphagia was the primary symptom in 17/26 (65%). In 85% (κ = 0.677) of cases, EGJ assessment (tight vs. open) was congruent between the combination of endoscopy (n = 26) and esophagram (n = 21) vs. EGJ-DI (n = 26) on FLIP. Follow-up data were available in 11 patients who had dilation based on a low EGJ-DI (4 with 20 mm balloon and 7 with ≥ 30 mm balloon). Overall, the mean % improvement in dysphagia was 60% (95% CI 37.7-82.3%, p = 0.0001). Nine out of 11 patients, including 6 out of 7 undergoing pneumatic dilation, had improvement ≥ 50% in dysphagia (mean % improvement 72.2%; 95% CI 56.1-88.4%, p = 0.0001). CONCLUSIONS AND INFERENCES: Functional lumen imaging probe is an accurate modality for evaluating for EGJ obstruction PF. FLIP may be used to select patients who may benefit from larger diameter dilation.

Esophagogastric Junction Distensibility on Functional Lumen Imaging Probe Topography Predicts Treatment Response in Achalasia-Anatomy Matters!

INTRODUCTION: 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. METHODS: 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). RESULTS: 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 of >5 cm was best associated with an ES of >3, 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 values < 0.0001 and 0.002). Using a DI cutoff of <2.8 as abnormal, 40 of 45 patients with retention (P = 0.0001) and 23 of 25 patients with an ES of >3 (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. DISCUSSION: 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.

The functional lumen imaging probe contractile response pattern is the best predictor of botulinum toxin response in esophagogastric junction outflow obstruction.

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

Relationship between dysphagia, lower esophageal sphincter relaxation, and esophagogastric junction distensibility.

BACKGROUND: It is debated whether high-resolution manometric (HRM) integrated relaxation pressure (IRP) or functional lumen imaging probe (FLIP) distensibility index (DI) is the superior measure of esophagogastric junction (EGJ) opening. We examined the relationship between the DI and IRP and assessed correlations with dysphagia symptoms in patients with achalasia and EGJ outflow obstruction (EGJOO). METHODS: Patients with achalasia and those with barium tablet retention at the EGJ were grouped as follows: Group 1:Achalasia (IRP ≥ 15 mmHg + complete absence of normal peristalsis); Group 2: Manometric +FLIP EGJOO (IRP ≥ 15 mmHg with some intact peristalsis + DI ≤ 2.8 mm2 /mmHg); Group 3: Abnormal DI only (DI ≤ 2.8 mm2 /mmHg + IRP <15 mmHg); and Group 4: Normal IRP and DI (IRP ≥ 15 mmHg + DI > 2.8 mm2 /mmHg). Correlation between the DI, baseline lower esophageal sphincter pressure (BLESP), IRP, and dysphagia (Eckardt score) was assessed. Multivariable analysis was used to assess variables associated with dysphagia score ≥2. KEY RESULTS: A total of 79 patients were included: Group 1 (n = 31), Group 2 (n = 33), Group 3 (n = 14), and Group 4 (n = 1). DI did not correlate with BLESP or IRP in the whole sample or subgroups. DI was the only variable associated with dysphagia score ≥2 (p = 0.006). DI < 1.25 mm2 /mmHg had sensitivity of 87% and specificity of 52% (p = 0.0003) for dysphagia score ≥2. CONCLUSIONS & INFERENCES: DI does not correlate with HRM EGJ measurements and is the metric with the strongest effect on dysphagia severity. The various biological elements that may cause restrictive EGJ function should be the subject of future studies.

Gas Leak and Mucosal Injury During Endoscopic Esophageal Myotomy After Previous Myotomy: A Single-Center Experience.

PURPOSE: Peroral endoscopic myotomy (POEM) after prior myotomy (PM-POEM) can be technically challenging with possible increased adverse events. We aimed to assess gas leak and mucosal injury incidence during PM-POEM, compared to an index POEM (iPOEM), and post-procedure extubation time. PATIENTS AND METHODS: A retrospective study comparing PM-POEM to iPOEM from March 2016 to August 2018. RESULTS: There were 21 subjects in the PM-POEM and 56 subjects in the iPOEM. The PM-POEM group was younger (average age 44.33 vs 57.57 years, p=0.0082). Gas leak incidence did not differ between groups (28.6% in PM-POEM vs 14.3% in iPOEM, p=0.148). For cases with imaging available postoperatively, there was a trend towards higher incidence of gas leak in the PM-POEM, but it was not statistically significant (60% vs 42.1%, p=0.359). The post-procedure extubation time was not different between PM-POEM and iPOEM (11.38 vs 9.46 minutes, p=0.93), but it was longer when gas leak occurred (15.92 vs 8.67 minutes, p=0.027). The odds of mucosal injury were four-fold higher (OR, 4.31; 95% CI, 1.32-14.08), and more clips were used to close mucosal injuries (0.62 vs 0.14 clips, p=0.0053) in the PM-POEM group. More procedures were deemed difficult or challenging in the PM-POEM (33.3% vs 7.1%, p=0.007). The number of clips used to close the mucosotomy was not different between groups (4.05 vs 3.84 clips, p=0.498). Although the myotomy was shorter in PM-POEM, it was not statistically significant (6.38 vs 7.14 cm, p=0.074). However, the procedure was longer in PM-POEM (61.28 vs 45.39 minutes, p=0.0017). There was no intervention or ICU admission required pertinent to the procedure. CONCLUSION: Performing PM-POEM can be more difficult with more mucosal injuries. Gas leak was associated with a slightly longer post-procedure extubation time, but clinical relevance is unclear given incidence of gas leak was unknown at time of extubation.