Esophageal Hypervigilance and Visceral Anxiety Contribute to Symptom Severity of Laryngopharyngeal Reflux.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is a clinical conundrum without a diagnostic gold standard. The Esophageal Hypervigilance and Anxiety Scale (EHAS) is a questionnaire designed for cognitive-affective evaluation of visceral sensitivity. We hypothesized that esophageal hypervigilance and symptom-specific anxiety have an etiopathological role in generation of LPR symptoms, especially when gastroesophageal reflux disease (GERD) cannot explain these symptoms. METHODS: Consecutive patients with LPR and/or GERD symptoms lasting >3 months were prospectively enrolled and characterized using the Reflux Symptom Index, GERD questionnaire, and EHAS. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring off acid suppression for phenotyping GERD and assessment of reflux burden, using conventional metrics (acid exposure time and number of reflux episodes) and novel metrics (mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index). RESULTS: Of 269 enrolled patients (mean age 47.1 years, 21-65 years, 60.6% female), 90 patients were with concomitant GERD and LPR symptoms, 32 patients were with dominant LPR symptoms, 102 patients were with dominant GERD symptoms, and 45 were controls. Patients with concomitant GERD and LPR symptoms had higher EHAS than those with dominant GERD symptoms and controls ( P ≤ 0.001); patients with dominant LPR symptoms had higher EHAS than controls ( P = 0.007). On Pearson correlation, EHAS positively correlated with the Reflux Symptom Index. DISCUSSION: Esophageal hypervigilance and symptom-specific anxiety may be more important than reflux burden in LPR symptom perception.

Question Prompt List as a Communication Tool for Adults With Gastroesophageal Reflux Disease: Incorporation of Patients' Perspectives.

BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, enhancing the patient-physician communication by encouraging patients to ask relevant questions during a consultation. Recently, a preliminary 78 question gastroesophageal reflux disease (GERD) specific QPL was created by 12 esophageal experts through a modified Delphi (RAND/University of California, Los Angeles) technique. Patients' perspectives and opinions on each question, however, had not been accounted for in the preliminary expert' version. AIM: The aim was to modify a preliminary experts' QPL, specific to adults with GERD, following patient perspectives and opinions. METHODS: A preliminary GERD QPL was modified through patient input and opinions. Thirty-eight patients with a clinical diagnosis of GERD followed at Stanford University Esophageal Clinic between January and November 2019 were consented to modify the preliminary 78 question expert QPL version. After receiving the QPL in Qualtrics (Provo, UT) by a direct e-mail invitation, patients independently rated questions on a 5-point Likert scale, where 1="should not be included," 2="unimportant," 3="don't know/depends," 4="important," and 5="essential." Questions were accepted for inclusion in the QPL with an a priori interagreement of 80% ranking in the range of 4 to 5. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?" RESULTS: Twenty-three patients with GERD (19 female, median age 64) fully participated and modified the existing QPL (60.5%). Of the 78 questions from the preliminary GERD QPL, 66 questions (84.6%) were accepted for inclusion. The question with the highest agreement among patients rating a question as essential consisted of "what habits, food, and drinks do I have to avoid?" (82.6%). Questions eliminated because of disagreement included "What is the natural history of GERD," "Do I have a high chance to die from my Barrett's?," and "Why are you prescribing an antidepressant to treat my GERD?" Nine patients suggested additional questions totaling to 16 separate questions, including "What type of surgeries are there to help GERD?," "What stage is my GERD?," "What are the odds/percentage of getting cancer from GERD?" Incorporating the suggested questions, the final GERD QPL-created by esophageal experts and modified by patients-consisted of 82 questions. CONCLUSION: Esophageal experts and GERD patients have a high level of agreement on important questions, though there is some variation in perspective. Future studies can simplify this list and measure the impact of a shared GERD QPL on patients' decisional conflict and perceived involvement in care.

How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery).

OBJECTIVE: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. DESIGN: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. RESULTS: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. CONCLUSION: With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.

Esophageal secondary peristalsis following acid infusion and chemical clearance correlate with mucosal integrity and acid sensitivity in GERD patients.

Background: Acid sensitivity can be altered in patients with gastroesophageal reflux disease (GERD). Secondary peristalsis helps clear gastro-esophageal refluxate and residual ingested food bolus. Objectives: The aim of this study was to investigate the associations among acid sensitivity, esophageal mucosal integrity, chemical clearance, and secondary peristalsis before and after esophageal acid infusion. Design: This was an investigator-initiated, prospective, cross-sectional study. Methods: Adult reflux patients underwent high resolution manometry and 24 h impedance-pH monitoring off acid suppression to identify GERD phenotypes, including non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Secondary peristalsis was assessed using five rapid 20 mL air injections into the esophagus before and after infusion of hydrochloric acid (0.1 N) into the mid-esophagus. Conventional acid infusion parameters recorded included lag time, intensity rating, and sensitivity score. Chemical clearance was evaluated using the post-reflux swallow-induced peristaltic wave (PSPW), and mucosal integrity was assessed by the mean nocturnal baseline impedance (MNBI) derived from impedance-pH monitoring. Results: A total of 88 patients (age 21-64 years, 62.5% women) completed the study including 12 patients with NERD, 45 with RH, and 31 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH, and FH. Upon acid infusion, patients who exhibited successful secondary peristalsis had longer lag time, higher MNBI, and shorter bolus contact time than those without secondary peristalsis. Meanwhile, patients with intact PSPW demonstrated significantly higher intensity ratings in response to acid perfusion and higher MNBI than those with impaired PSPW. The lag time correlated positively with MNBI (r = 0.285; p = 0.007). Conclusion: In conclusion, the protective effect of esophageal secondary peristalsis and chemical clearance on esophageal mucosal integrity was demonstrated. Concerning acid sensitivity, longer lag time in patients with intact secondary peristalsis may be attributed to better esophageal mucosal integrity, while stronger intensity ratings may have a greater tendency to induce PSPW and protect esophageal mucosal integrity.

Analysis of contractile segment impedance during straight leg raise maneuver using high-resolution impedance manometry increases diagnostic yield in reflux disease.

BACKGROUND: Contractile segment impedance (CSI) obtained from high-resolution impedance manometry (HRIM) is a measure of mucosal integrity that predicts gastroesophageal reflux disease (GERD). While straight leg raise (SLR) maneuver augments esophageal peristaltic vigor, it remains unclear whether SLR affects CSI values. This study was aimed to evaluate whether CSI with SLR is feasible and useful to complement the diagnosis of GERD. METHODS: We prospectively recruited 48 patients with typical GERD symptoms who underwent esophagogastroduodenoscopy, HRIM with SLR maneuver, and multichannel intraluminal impedance-pH (MII-pH) testing. The capability of mean nocturnal baseline impedance (MNBI), resting baseline impedance (RBI), CSI with or without SLR maneuver in predicting GERD was assessed using receiver operating characteristics (ROC) analysis. KEY RESULTS: Among 20 GERD patients and 28 non-GERD patients, all values of impedance-based metrics were lower in GERD patients compared to non-GERD patients (p < 0.001). For GERD identification, area under receiver operating characteristic curve (AUROC) values of CSI with SLR maneuver, CSI, MNBI, and RBI were 0.901, 0.858, 0.865, and 0.797. Particularly in ineffective esophageal motility (IEM) patients, SLR maneuver increased mean distal contractile integral from 436 to 828.7 mmHg.s.cm (p = 0.018) and enhanced AUROC values of CSI for GERD identification from 0.917 to 0.958. CONCLUSIONS & INFERENCES: CSI measurement during HRIM appears to be a reliable, time-saving, and less invasive tool for complementing GERD diagnosis. Our results also suggest a simple SLR maneuver during HRIM could enhance diagnostic accuracy of CSI for GERD identification especially in IEM patients.

Oesophageal hypervigilance and visceral anxiety relate to reflux symptom severity and psychological distress but not to acid reflux parameters.

BACKGROUND: The pathogenesis of gastro-oesophageal reflux disease (GERD) is complex and multifactorial. The oesophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive-affective evaluation of visceral sensitivity. AIMS: To investigate the interrelationship between EHAS and reflux symptom severity, psychological stress, acid reflux burden, phenotypes, and oesophageal mucosal integrity in patients with GERD. METHODS: Patients with chronic reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, acid reflux burden, and mucosal integrity with mean nocturnal baseline impedance (MNBI) calculation. Validated scores for patient-reported outcomes, including EHAS, GERD questionnaire (GERDQ), State-Trait Anxiety Inventory score, and Taiwanese Depression Questionnaire score, were recorded. RESULTS: We enrolled 105 patients, aged 21-64 years (mean, 48.8), of whom 58.1% were female; 27 had non-erosive reflux disease, 43 had reflux hypersensitivity and 35 had functional heartburn. There were no significant differences in sex, EHAS, GERDQ, questionnaires of depression or anxiety among GERD phenotypes. EHAS was significantly correlated with GERDQ, questionnaires of depression and anxiety (P < 0.05). However, there were no significant correlations between GERDQ and questionnaires of depression or anxiety. Regarding patient-reported outcomes, GERDQ positively correlated with acid exposure time and negatively correlated with MNBI (P < 0.05). CONCLUSIONS: EHAS associates with reflux symptom severity and psychological stress but not with acid reflux burden or mucosal integrity. Thus, EHAS assessment shows promise in assessment of subjective patient outcome and satisfaction with treatment, a hitherto unmet clinical need.

Impact of ineffective esophageal motility on secondary peristalsis: Studies with high-resolution manometry.

BACKGROUND/AIM: The aim was to investigate whether there is a difference in secondary peristalsis on high-resolution manometry (HRM) among gastroesophageal reflux disease (GERD) patients with and without ineffective esophageal motility (IEM), and healthy individuals. METHODS: Twenty-eight GERD patients and seventeen healthy controls were included. Secondary peristalsis was stimulated by a rapid injection of 20 ml air in mid-esophagus. We compared HRM metrics and the response and effective rate of triggering secondary peristalsis between patients with and without IEM and healthy controls. RESULTS: Sixteen patients had IEM, and the remaining 12 had normal manometry. By triggering of secondary peristalsis, patients without IEM and healthy controls had significantly higher distal contractile integral (DCI) values than IEM patients (p = 0.006). A successful secondary peristalsis was triggered more frequently in healthy controls than in GERD patients with normal peristalsis or IEM (56.9% vs. 20.2% vs. 9.1%, all p < 0.001). The effective rate which determined as DCI > 450 mm Hg.cm.s was higher in healthy controls compared to patients with normal peristalsis (36.5% vs. 19.4%, p < 0.001) and IEM (36.5% vs. 6.3%, p < 0.001). Patients with IEM had lower successful triggering response (9.1% vs. 20.2%) and effective secondary peristalsis (6.3% vs. 19.4%) compared with patients without IEM (p < 0.001). CONCLUSIONS: Our work has demonstrated that GERD patients, in particular those with IEM, have significant defects in the triggering of secondary peristalsis on HRM. HRM helps characterize esophageal secondary peristalsis which exhibits differently in patients with and without IEM.

Endoscope presence during endoluminal functional lumen imaging probe (FLIP) influences FLIP metrics in the evaluation of esophageal dysmotility.

BACKGROUND: The functional lumen imaging probe (FLIP) system is an FDA-approved tool for dynamic evaluation of the esophagogastric junction (EGJ). Even though commercially available since 2009, FLIP utilization remains low, partly due to lack of consensus in methodology and interpretation. Therefore, we aimed to analyze the influence of concurrent endoscopy on FLIP measurements. METHODS: In this single-center study, we reviewed data from 93 patients undergoing FLIP for symptomatic esophageal motility disorders between 2016 and 2018. During sedated endoscopy, we measured luminal values (distensibility, cross-sectional area (CSA), and balloon pressure) at the EGJ and distal esophagus using 30, 40, and 50 mL distension volumes, with and without concurrent endoscope presence. All recorded values were compared at the various distension volumes between the two measurements using a Wilcoxon rank sum test. KEY RESULTS: There was a significant difference in distensibility and CSA with index distension volume (40 mL) at the EGJ comparing the two measurements: Lower median distensibility was 2.1 mm2  mm Hg-1 in the group with concurrent inserted endoscope, respectively, 3.4 mm2  mm Hg-1 without endoscope (P < .001), and median CSA was 86.0 resp. 110.0 mm2 (P < .001). No significant difference could be found in the measurements of the distal esophagus. CONCLUSIONS & INFERENCES: Our results show a significant difference in FLIP measurements with and without endoscope presence. This underlines the importance of establishing a consensus of a standardized FLIP protocol to define normal luminal values and guiding future FLIP diagnostic studies.

Correlation between reflux burden, peristaltic function, and mucosal integrity in GERD patients.

BACKGROUND: Mean nocturnal baseline impedance (MNBI) augments the diagnostic yield of multichannel intraluminal impedance-pH (MII-pH) monitoring. While acid exposure time (AET) correlates with MNBI, it remains unclear whether esophageal motility affects MNBI values. The present study was aimed at evaluating the respective roles of esophageal motor function and AET on MNBI. METHODS: High-resolution manometry (HRM) studies and ambulatory 24-hour MII-pH monitoring tracings were retrospectively analyzed from consecutive endoscopy-negative GERD patients with typical symptoms responsive to previous acid-suppressive therapy from three tertiary care centers. Univariate and multivariate analyses were performed to determine predictors of pathologic MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES). KEY RESULTS: Patients with pathological AET displayed lower MNBI values at 3 cm and 5 cm (P < .01) compared to patients with non-pathological AET. Similarly, significantly lower MNBI values were also noted at both sites with type 3 EGJ compared to type 1 EGJ (P ≤ .02 for each comparison), and with absent contractility compared to normal peristalsis (P ≤ .02 for each comparison). On multivariate analysis, the presence of type 2 or 3 EGJ and absent contractility were associated with a significantly higher probability of pathological MNBI values at 3 cm and 5 cm above the LES. CONCLUSIONS AND INFERENCES: Disruption of the EGJ and absent contractility on HRM are both associated with lower MNBI values. HRM findings complement reflux testing using MII-pH monitoring.

The impact of opiate pain medications and psychoactive drugs on the quality of colon preparation in outpatient colonoscopy.

BACKGROUND: Suboptimal colon preparation is a significant barrier to quality colonoscopy. The impact of pharmacologic agents associated with gastrointestinal dysmotility on quality of colon preparation has not been well characterized. AIMS: Evaluate impact of opiate pain medication and psychoactive medications on colon preparation quality in outpatients undergoing colonoscopy. METHODS: Outpatients undergoing colonoscopy at a single medical centre during a 6-month period were retrospectively identified. Demographics, clinical characteristics and pharmacy records were extracted from electronic medical records. Colon preparation adequacy was evaluated using a validated composite colon preparation score. RESULTS: 2600 patients (57.3 ± 12.9 years, 57% female) met the inclusion and exclusion criteria. 223 (8.6%) patients were regularly using opioids, 92 antipsychotics, 83 tricyclic antidepressants and 421 non-tricyclic antidepressants. Opioid use was associated with inadequate colon preparation both with low dose (OR = 1.4, 95%CI 1.0-2.1, p = 0.05) and high dose opioid users (OR = 1.7, 95%CI 1.1-2.9, p = 0.039) in a dose dependent manner. Other significant predictors of inadequate colon preparation included use of tricyclics (OR = 1.9, 95%CI 1.1-3.0, p = 0.012), non-tricyclic antidepressants (OR = 1.5, 95%CI 1.1-2.0, p = 0.013), and antipsychotic medications (OR = 2.2, 95%CI 1.4-3.4, p = 0.001). CONCLUSIONS: Opiate pain medication use independently predicts inadequate quality colon preparation in a dose dependent fashion; furthermore psychoactive medications have even more prominent effects and further potentiates the negative impact of opiates with concurrent use.