Esophageal Motility Disorders: Current Approach to Diagnostics and Therapeutics.

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.

Opioid Exposure Differentially Impacts Esophageal Body Contraction Over the Lower Esophageal Sphincter.

BACKGROUND & AIMS: Studies with limited sample sizes have investigated association of chronic opioid use with motility disorders of esophagogastric junction and esophageal body peristalsis. Our aims were to use a large cohort of patients to assess (1) the impact of opioid exposure on clinical and manometric characteristics, and (2) the association of opioid exposure with higher long-term symptom burden. METHODS: Patients recruited from a tertiary medical center who underwent high-resolution manometry (HRM) between 2007 and 2018 were included. Demographics, opiate exposure, clinical symptoms, and HRM parameters were compared. Patient-Reported Outcomes Measurement Information System-Gastrointestinal swallowing domain (PROMIS-GI swallowing domain) and Eckardt score were administered via phone interviews in patients with hypercontractile esophagus (HE) or distal esophageal spasm (DES) to determine long-term symptom burden between opioid and nonopioid users. RESULTS: Our cohort included 4075 patients (869 with opiate exposure with median morphine milligram equivalent [interquartile range] of 30 [10-45]). Patients in the opioid group were significantly more likely to have dysphagia (65% vs 51%, P < .01) and diagnosis of DES (11% vs 5%, P < .01) and HE (9% vs 3%, P < .01). Partial opioid agonists were not associated with motility abnormalities. Patients on opioids had significantly higher symptom burden on median (interquartile range) follow-up of 8.9 years (5.8-10.4) post manometric diagnosis with median PROMIS-GI swallowing domain score of 21.5 (17-25) compared with the nonopioid group at 15 (9.8-21, P = .03). CONCLUSIONS: Nearly 2 of 3 patients with opioid exposure undergoing HRM have dysphagia and more than 25% of them with dysphagia as the primary symptom have a diagnosis of either DES or HE. Opioid users with spastic disorders have higher symptom burden long-term compared with nonopioid users.

Development and Validation of a Mucosal Impedance Contour Analysis System to Distinguish Esophageal Disorders.

BACKGROUND & AIMS: Diagnostic testing for chronic esophageal disorders relies on histopathology analysis of biopsies or uncomfortable transnasal catheters or wireless pH monitoring, which capture abnormal intraluminal refluxate. We therefore developed a balloon mucosal impedance (MI) catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy over a long segment of the esophagus. We performed a prospective study to evaluate the ability of a balloon-incorporated MI catheter to detect and evaluate esophageal disorders, including gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE). METHODS: We performed a prospective study of 69 patients undergoing esophagogastroduodenoscopy with or without wireless pH monitoring. Patients were classified as having GERD (erosive esophagitis or abnormal pH; n = 24), EoE (confirmed with pathology analysis of tissues from both distal and proximal esophagus; n = 21), or non-GERD (normal results from esophagogastroduodenoscopy and pH tests; n = 24). Receiver operating characteristic curves and area under the operating characteristic curve (AUC) were used to compare the accuracy of balloon MI in diagnosis. Probabilities of assignment to each group (GERD, non-GERD, or EoE) were estimated using multinomial logistic regression. Association between MI patterns and diagnoses were validated using data from patients seen at 3 separate institutions. RESULTS: MI pattern along the esophageal axis differed significantly (P < .01) among patients with GERD, EoE, and non-GERD. Patients with non-GERD had higher MI values along all measured segments. The MI pattern for GERD was easily distinguished from that of EoE: in patients with GERD, MI values were low in the distal esophagus and normalized along the proximal esophagus, whereas in patients with EoE, measurements were low in all segments of the esophagus. Intercept and rate of rise of MI value (slope) as distance increased from the squamocolumnar junction identified patients with GERD with an AUC = 0.67, patients with EoE with an AUC = 0.84, and patients with non-GERD with an AUC = 0.83 in the development cohort. One patient had an adverse event (reported mild chest pain after the procedure) and was discharged from the hospital without further events. CONCLUSIONS: We developed a balloon MI catheter system that instantly detects changes in esophageal mucosal integrity during endoscopy and found it to be safe and able to identify patients with GERD, EoE, or non-GERD. We validated our findings in a separate cohort for patients. ClinicalTrials.gov ID NCT03103789.

Model to Select On-Therapy vs Off-Therapy Tests for Patients With Refractory Esophageal or Extraesophageal Symptoms.

BACKGROUND & AIMS: It is not clear whether we should test for reflux in patients with refractory heartburn or extraesophageal reflux (EER) symptoms, such as cough, hoarseness, or asthma. Guidelines recommend testing patients by pH monitoring when they are on or off acid-suppressive therapies based on pretest probability of reflux, determined by expert consensus. However, it is not clear what constitutes a low or high pretest probability of reflux in these patients. We aimed to develop a model that clinicians can use at bedside to estimate pretest probability of abnormal reflux. METHODS: We performed a prospective study of 471 adult patients with refractory heartburn (n = 214) or suspected EER symptoms (n = 257) who underwent endoscopy with wireless pH monitoring while they were off acid-suppressive treatment and assigned them to groups based on symptoms at presentation (discovery cohort). Using data from the discovery cohort, we performed proportional odds ordinal logistic regression to select factors (easy to obtain demographic criteria and clinical symptoms such as heartburn, regurgitation, asthma, cough, and hoarseness) associated with esophageal exposure to acid. We validated our findings in a cohort of 118 patients with the same features from 2 separate tertiary care centers (62% women; median age 59 years; 62% with cough as presenting symptom). RESULTS: Abnormal pH (>5.5% of time spent at pH <4) was found in 56% of patients with heartburn and 63% of patients with EER (P = .15). Within EER groups, abnormal pH was detected in a significantly larger proportion (80%) of patients with asthma compared with patients with cough (60%) or hoarseness (51%; P < .01). Factors significantly associated with abnormal pH in patients with heartburn were presence of hiatal hernia and body mass index >25 kg/m2. In patients with EER, the risk of reflux was independently associated with the presence of concomitant heartburn (odds ratio [OR] 2.0; 95% confidence interval [CI] 1.3-3.1), body mass index >25 kg/m2 (OR 2.1; 95% CI 1.5-3.1), asthma (OR 2.0; 95% CI 1.2-3.5), and presence of hiatal hernia (OR 1.9; 95% CI 1.2-3.1). When we used these factors to create a scoring system, we found that a score of ≤2 excluded patients with moderate to severe reflux, with a negative predictive value of 80% in the discovery cohort and a negative predictive value of 85% in the validation cohort. CONCLUSION: We developed a clinical model to estimate pretest probability of abnormal pH in patients who were failed by proton pump inhibitor therapy. This system can help guide clinicians at bedside in determining the most appropriate diagnostic test in this challenging group of patients.

Utility of esophageal mucosal impedance as a diagnostic test for esophageal disease.

PURPOSE OF REVIEW: The aim of this review is to summarize the use of direct mucosal impedance (MI) for the evaluation and management of esophageal diseases. RECENT FINDINGS: Esophageal multichannel intraluminal impedance with pH (MII-pH) monitoring has been considered the most sensitive test for gastroesophageal reflux disease (GERD), but recent studies have failed to establish impedance parameters that reliably predict treatment response to medical and surgical GERD therapies. MII-pH uses a catheter passed through the nose, which is uncomfortable for patients, and the test is compromised by the day-to-day variability of reflux patterns. Recently, an MI device has been developed that can be passed through the working channel of an endoscope to measure esophageal epithelial conductivity as a marker of chronic GERD. The MI values so obtained are available within seconds, correlate with histological findings of epithelial barrier dysfunction, normalize with effective treatment, and show promise for diagnosing eosinophilic esophagitis and for distinguishing it from GERD. SUMMARY: MI can differentiate esophageal disorders instantly during endoscopy, and can monitor treatment responses in GERD and eosinophilic esophagitis.

Oropharyngeal Reflux Monitoring and Atypical Gastroesophageal Reflux Disease.

The prevalence of gastroesophageal reflux disease (GERD) has been increasing since the 1990 s, with up to 27.8 % of people in North America affected by this disorder. The healthcare burden of patients who primarily have extra-esophageal manifestations of GERD (atypical GERD) is estimated to be 5 times that of patients with primarily heartburn and regurgitation due to lack of a gold standard diagnostic test, poor responsiveness to PPI therapy, and delay in recognition. Empiric twice daily PPI therapy for 1-2 months is currently considered the best diagnostic test, but due to poor responsiveness to PPIs in patients with atypical GERD in multiple randomized controlled trials, newer modes of diagnostic procedures such as oropharyngeal pH monitoring have gained significantly more traction. The utility of oropharyngeal pH monitoring systems such as Restech Dx-pH is currently limited due to lack of consensus on normal and abnormal cutoff values. Recent studies suggest its utility as a prognostic tool and its ability to predict responsiveness to medical and surgical therapy. However, routine use of oropharyngeal pH monitoring is still not widespread due to the lack of well-controlled prospective studies.

Laryngopharyngeal Reflux and Functional Laryngeal Disorder: Perspective and Common Practice of the General Gastroenterologist.

Laryngopharyngeal reflux (LPR) is an extraesophageal variant of gastroesophageal reflux disease that is associated with chronic cough, hoarseness, dysphonia, recurrent throat clearing, and globus pharyngeus. Due to nonspecific symptoms, laryngoscopy is often performed to rule out malignancy, and the diagnosis of LPR is considered with any signs of laryngeal inflammation. However, laryngoscopic findings have high interobserver variability, and, thus, most patients are tried on an empiric course of acid-suppressive therapy to see whether symptoms resolve. In this article, which focuses on the perspective and common practice of the general gastroenterologist, we review our understanding of the pathophysiology, diagnosis, and treatment of LPR based on important clinical articles in the gastroenterology literature. We also propose new diagnostic criteria for functional laryngeal disorder and review laryngeal hypersensitivity and treatment options for general gastroenterologists.

An Overview of Achalasia and Its Subtypes.

Achalasia is one of the most studied esophageal motility disorders. However, the pathophysiology and reasons that patients develop achalasia are still unclear. Patients often present with dysphagia to solids and liquids, regurgitation, and varying degrees of weight loss. There is significant latency prior to diagnosis, which can have nutritional implications. The diagnosis is suspected based on clinical history and confirmed by esophageal high-resolution manometry testing. Esophagogastroduodenoscopy is necessary to rule out potential malignancy that can mimic achalasia. Recent data presented in abstract form suggest that patients with type II achalasia may be most likely, and patients with type III achalasia may be least likely, to report weight loss compared to patients with type I achalasia. Although achalasia cannot be permanently cured, palliation of symptoms is possible in over 90% of patients with the treatment modalities currently available (pneumatic dilation, Heller myotomy, or peroral endoscopic myotomy). This article reviews the clinical presentation, diagnosis, and management options in patients with achalasia, as well as potential insights into histopathologic differences and nutritional implications of the subtypes of achalasia.

Patient-Reported Outcome Measures Related to Laryngopharyngeal Reflux: A Systematic Review of Instrument Development and Validation.

OBJECTIVES: Patient-reported outcome (PRO) measures are often used to diagnose laryngopharyngeal reflux (LPR) and monitor treatment outcomes in clinical and research settings. The present systematic review was designed to identify currently available LPR-related PRO measures and to evaluate each measure's instrument development, validation, and applicability. DATA SOURCES: MEDLINE via PubMed interface, CINAHL, and Health and Psychosocial Instrument databases were searched with relevant vocabulary and key terms related to PRO measures and LPR. REVIEW METHODS: Three investigators independently performed abstract review and full text review, applying a previously developed checklist to critically assess measurement properties of each study meeting inclusion criteria. RESULTS: Of 4947 studies reviewed, 7 LPR-related PRO measures (publication years, 1991-2010) met criteria for extraction and analysis. Two focused on globus and throat symptoms. Remaining measures were designed to assess LPR symptoms and monitor treatment outcomes in patients. None met all checklist criteria. Only 2 of 7 used patient input to devise item content, and 2 of 7 assessed responsiveness to change. Thematic deficiencies in current LPR-related measures are inadequately demonstrated: content validity, construct validity, plan for interpretation, and literacy level assessment. CONCLUSION: Laryngopharyngeal reflux is often diagnosed according to symptoms. Currently available LPR-related PRO measures used to symptomatically identify suspected LPR patients have disparate developmental rigor and important methodological deficiencies. Care should be exercised to understand the measurement characteristics and contextual relevance before applying these PRO measures for clinical, research, or quality initiatives.

Idiopathic (primary) achalasia: a review.

Idiopathic achalasia is a primary esophageal motor disorder characterized by loss of esophageal peristalsis and insufficient lower esophageal sphincter relaxation in response to deglutition. Patients with achalasia commonly complain of dysphagia to solids and liquids, bland regurgitation often unresponsive to an adequate trial of proton pump inhibitor, and chest pain. Weight loss is present in many, but not all patients. Although the precise etiology is unknown, it is often thought to be either autoimmune, viral immune, or neurodegenerative. The diagnosis is based on history of the disease, barium esophagogram, and esophageal motility testing. Endoscopic assessment of the gastroesophageal junction and gastric cardia is necessary to rule out malignancy. Newer diagnostic modalities such as high resolution manometry help in predicting treatment response in achalasia based on esophageal pressure topography patterns identifying three phenotypes of achalasia (I-III) and outcome studies suggest better treatment response with types I and II compared to type III. Although achalasia cannot be permanently cured, excellent outcomes are achieved in over 90 % of patients. Current medical and surgical therapeutic options (pneumatic dilation, endoscopic and surgical myotomy, and pharmacologic agents) aim at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Either graded pneumatic dilatation or laparoscopic surgical myotomy with a partial fundoplication are recommended as initial therapy guided by patient age, gender, preference, and local institutional expertise. The prognosis in achalasia patients is excellent. Most patients who are appropriately treated have a normal life expectancy but the disease does recur and the patient may need intermittent treatment.