Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by an immune response that leads to symptoms of dysphagia, chest pain, and food impaction. EoE is a clinicopathologic syndrome that requires clinical symptoms and pathologic findings for a diagnosis. The inflammatory process and eosinophilic infiltration of the esophagus in EoE lead to fibrosis and structural changes within the esophagus that cause esophageal dysfunction. The biomechanics of the esophageal function in EoE have been explored using manometry, impedance planimetry, barium esophagograms, and endoscopic ultrasound. These studies have identified several biomechanical changes to the esophagus in EoE including pan-esophageal pressurization on manometry, changes in esophageal compliance with decreased distentisbility by impedance planimetry, decreased esophageal luminal diameter by esophagograms, and dysfunction in the esophageal longitudinal muscles by endoscopic ultrasound. Treatments for the disease involve dietary changes, immunosuppressive drugs, and dilation techniques. However, the data regarding the effect of these therapies on altering mechanical properties of the esophagus is limited. As the pathogenesis of esophageal dysfunction in EoE appears multifactorial, further study of the biomechanics of EoE is critical to better diagnose, monitor and treat the disease.
Barium ; Biomechanics ; Chest Pain ; Compliance ; Deglutition Disorders ; Dilatation ; Electric Impedance ; Eosinophilic Esophagitis ; Eosinophils ; Esophagus ; Fibrosis ; Manometry ; Muscles ; Organothiophosphorus Compounds ; Phenobarbital

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Manometry

Background/Aims: Jackhammer esophagus is an uncommon heterogeneous motility disorder associated with a distal contractile integral > 8000 mmHg · sec · cm. The spectrum of abnormality ranges from a relatively normal looking contraction to chaotic repetitive contractions akin to a jackhammer. Although previous studies have shown an uncertain correlation between peristaltic vigor and symptoms, we hypothesize that symptoms may be more severe with repetitive contractions as opposed to an elevated contractile measure. Thus, this study aims to investigate whether symptom severity is related to the contraction pattern in the patients with hypercontractile esophagus. Methods: Patients with hypercontractile esophagus were retrospectively identified, their demographic and high-resolution manometry characteristics were collected. Contraction pattern on high-resolution manometry was categorized into single-peak and multiple-peak.Comparison was performed between patients with single-peak and multiple-peak. Results: Altogether 35 patients (age range, 45-70 years; female:male, 24:11) were included. Seven patients presented with single-peak hypercontractile swallows, while 28 patients presented with multiple-peak hypercontractile swallows. The patients with multiple-peak showed higher Brief Esophageal Dysphagia Questionnaire scores compared with patients with single-peak. The jackhammer swallows with multiple-peak were associated with higher distal contractile integral values, longer distal latency intervals, and a lower integrated relaxation pressure. Conclusions Repetitive contractions akin to a jackhammer were common amongst patients with hypercontractile esophagus. Patients with the jackhammer pattern also presented with more severe symptoms. Further distinction of hypercontractile esophagus into a jackhammer dominant subtype may be warranted.

Background/Aims: Jackhammer esophagus is an uncommon heterogeneous motility disorder associated with a distal contractile integral > 8000 mmHg · sec · cm. The spectrum of abnormality ranges from a relatively normal looking contraction to chaotic repetitive contractions akin to a jackhammer. Although previous studies have shown an uncertain correlation between peristaltic vigor and symptoms, we hypothesize that symptoms may be more severe with repetitive contractions as opposed to an elevated contractile measure. Thus, this study aims to investigate whether symptom severity is related to the contraction pattern in the patients with hypercontractile esophagus. Methods: Patients with hypercontractile esophagus were retrospectively identified, their demographic and high-resolution manometry characteristics were collected. Contraction pattern on high-resolution manometry was categorized into single-peak and multiple-peak.Comparison was performed between patients with single-peak and multiple-peak. Results: Altogether 35 patients (age range, 45-70 years; female:male, 24:11) were included. Seven patients presented with single-peak hypercontractile swallows, while 28 patients presented with multiple-peak hypercontractile swallows. The patients with multiple-peak showed higher Brief Esophageal Dysphagia Questionnaire scores compared with patients with single-peak. The jackhammer swallows with multiple-peak were associated with higher distal contractile integral values, longer distal latency intervals, and a lower integrated relaxation pressure. Conclusions Repetitive contractions akin to a jackhammer were common amongst patients with hypercontractile esophagus. Patients with the jackhammer pattern also presented with more severe symptoms. Further distinction of hypercontractile esophagus into a jackhammer dominant subtype may be warranted.

Background/Aims: Cholecystokinin (CCK) administration has been shown to reduce lower esophageal sphincter (LES) pressure in normal subjects in manometric studies. Functional luminal imaging probe (FLIP) panometry offers a method to assess esophageal motility in response to sustained distension though mechanisms related to this response remain unexplored. The aim of this study is to evaluate the effect of CCK-8 on the esophageal response to distension in asymptomatic volunteers using FLIP. Methods: Esophageal response to distension was studied in 7 asymptomatic volunteers (mean age ± SD [27 ± 2]; 86% female) before and after CCK-8 administration in a crossover study design. During sedated endoscopy, FLIP was performed twice with CCK-8 administered via intravenous push in one of 2 protocols: during filling (n = 4) or during emptying (n = 3). Esophagogastric junction distensibility index (EGJ-DI) at 60 mL fill volume and esophageal body contractile response patterns were analyzed. Results: During the baseline FLIP study, all subjects had a contractile response with repetitive antegrade contractions both before and after CCK-8 administration. However, a sustained LES contraction or a sustained occluding contraction with esophageal shortening was observed in all subjects in the filling protocol, but in none during the emptying protocol. EGJ-DI was similar before and after CCK-8 during both filling (4.7 ± 1.9 mm2 /mmHg vs 4.3 ± 1.8 mmmm2 /mmHg) and emptying protocol (7.5 ± 1.4 mmmm2 /mmHg vs 6.9 ± 0.6 mmmm2 /mmHg). Conclusion While EGJ-DI appeared unaffected by CCK-8 administration in asymptomatic volunteers, CCK induced spastic-reactive contractions of the LES during distention suggesting that exogenous CCK interferes with normal LES relaxation during secondary peristalsis.

Background/Aims: This study aimed to develop a diagnostic tool using machine learning to apply functional luminal imaging probe (FLIP) panometry data to determine the probability of esophagogastric junction (EGJ) obstruction as determined using the Chicago Classification version 4.0 (CCv4.0) and high-resolution manometry (HRM). Methods: Five hundred and fifty-seven adult patients that completed FLIP and HRM (with a conclusive CCv4.0 assessment of EGJ outflow) and 35 asymptomatic volunteers (“controls”) were included. EGJ opening was evaluated with 16-cm FLIP performed during sedated endoscopy via EGJ-distensibility index and maximum EGJ diameter. HRM was classified according to the CCv4.0 as conclusive disorders of EGJ outflow or normal EGJ outflow (timed barium esophagram applied when required and available). The probability tool utilized Bayesian additive regression treesBART, which were evaluated using a leave-one-out approach and a holdout test set. Results: Per HRM and CCv4.0, 243 patients had a conclusive disorder of EGJ outflow while 314 patients (and all 35 controls) had normal EGJ outflow. The model accuracy to predict EGJ obstruction (based on leave-one-out/holdout test set, respectively) was 89%/90%, with 87%/85% sensitivity, 92%/97% specificity, and an area under the receiver operating characteristic curve of 0.95/0.97. A free, opensource tool to calculate probability for EGJ obstruction using FLIP metrics is available at https://www.wklytics.commgi/prob_flip.html. Conclusions Application of FLIP metrics utilizing a probabilistic approach incorporates the diagnostic confidence (or uncertainty) into the clinical interpretation of EGJ obstruction. This tool can provide clinical decision support during application of FLIP Panometry for evaluation of esophageal motility disorders.

Background/Aims: Incorporation of complementary and provocative test swallows to the high-resolution manometry (HRM) protocol offers potential to address limitations posed by HRM protocols that involve only a single swallow type. The aim of this study is to describe normal findings of a comprehensive HRM testing protocol performed on healthy asymptomatic volunteers. Methods: Thirty healthy asymptomatic volunteers completed HRM with 5-mL liquid swallows in the supine position. They also completed 5-mL liquid swallows in the upright position, viscous swallows, solid test swallows, multiple rapid swallows, and a rapid drink challenge.HRM studies were analyzed via Chicago classification version 3.0. Results: The median (5th-95th percentiles) for integrated relaxation pressure (IRP) on supine swallows was 11 (4-16) mmHg; IRP was lower than supine on upright liquid 9 (0-17) mmHg, viscous 6 (0-15) mmHg, solid 9 (1-19) mmHg, multiple rapid swallows 3 (0-12) mmHg, and rapid drink challenge 5 (–3-12) mmHg; P < 0.005. While an “elevated” IRP value was observed on 1 to 2 test maneuvers in 8/30 (27%) subjects, all 30 subjects had an IRP value < 12 mmHg on at least one of the test maneuvers. Conclusions Normal values and findings from a comprehensive HRM testing protocol are reported based on evaluation of 30 healthy asymptomatic volunteers. Isolated “abnormalities” of IRP and contractile parameters were observed in the majority (80%) of these asymptomatic subjects, while all subjects also had normal features observed. Thus, the definition of “normal” should be recalibrated to focus on the entirety of the study and not individual metrics.

Background/Aims: Incorporation of complementary and provocative test swallows to the high-resolution manometry (HRM) protocol offers potential to address limitations posed by HRM protocols that involve only a single swallow type. The aim of this study is to describe normal findings of a comprehensive HRM testing protocol performed on healthy asymptomatic volunteers. Methods: Thirty healthy asymptomatic volunteers completed HRM with 5-mL liquid swallows in the supine position. They also completed 5-mL liquid swallows in the upright position, viscous swallows, solid test swallows, multiple rapid swallows, and a rapid drink challenge.HRM studies were analyzed via Chicago classification version 3.0. Results: The median (5th-95th percentiles) for integrated relaxation pressure (IRP) on supine swallows was 11 (4-16) mmHg; IRP was lower than supine on upright liquid 9 (0-17) mmHg, viscous 6 (0-15) mmHg, solid 9 (1-19) mmHg, multiple rapid swallows 3 (0-12) mmHg, and rapid drink challenge 5 (–3-12) mmHg; P < 0.005. While an “elevated” IRP value was observed on 1 to 2 test maneuvers in 8/30 (27%) subjects, all 30 subjects had an IRP value < 12 mmHg on at least one of the test maneuvers. Conclusions Normal values and findings from a comprehensive HRM testing protocol are reported based on evaluation of 30 healthy asymptomatic volunteers. Isolated “abnormalities” of IRP and contractile parameters were observed in the majority (80%) of these asymptomatic subjects, while all subjects also had normal features observed. Thus, the definition of “normal” should be recalibrated to focus on the entirety of the study and not individual metrics.

Background/Aims: High-resolution manometry (HRM) performed without sedation is the standard procedure. However, some patients cannot tolerate transnasal placement of the manometry catheter. We aim to assess the practice of performing manometry after endoscopy with conscious sedation by evaluating its impact on esophageal motility findings. Methods: Twelve asymptomatic adult volunteers and 7 adult patients completed high-resolution impedance manometry (HRIM) approximately 1 hour after conscious sedation with midazolam and fentanyl (post-sedation) and again on a different day with no-sedation. The nosedation HRIM involved 2 series of swallows separated in time by 20 minutes (no-sedation-1 and no-sedation-2) for the volunteers; patients completed only 1 series of swallows for no-sedation HRM. Results: A motility diagnosis of normal motility was observed in all 12 volunteers post-sedation. Two volunteers had a diagnosis of borderline ineffective esophageal motility, one during the no-sedation-1 period and the other during the no-sedation-2 period; all of the other no-sedation HRIM studies yielded a normal motility diagnosis. Six of seven patients had the same diagnosis in both no-sedation and post-sedation HRM, including 1 distal esophageal spasm, 3 achalasia (2 type II and 1 type III), and 2 esophagogastric junction outflow obstruction. Only one patient’s HRM classification changed from ineffective esophageal motility at no-sedation to normal esophageal motility at post-sedation. Conclusions Performing HRIM after endoscopy with conscious sedation had minimal clinical impact on the motility diagnosis or motility parameters. Thus, this approach may be a viable alternative for patients who cannot tolerate unsedated catheter placement.