Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients' outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38-57 years]) with a diagnosis of functional heartburn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index >= 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients' management

Minimally invasive endoscopic therapies for gastro-oesophageal reflux disease

The prevalence of the gastro-oesophageal reflux disease (GORD) in the western world is increasing. Uncontrolled GORD can lead to harmful long-term sequela such as oesophagitis, stricture formation, Barrett's oesophagus and oesophageal adenocarcinoma. Moreover, GORD has been shown to negatively impact quality of life. The current treatment paradigm for GORD consists of lifestyle modification, pharmacological control of gastric acid secretion or antireflux surgery. In recent years, several minimally invasive antireflux endoscopic therapies (ARET) have been developed which may play a role in bridging the unmet therapeutic gap between the medical and surgical treatment options. To ensure optimal patient outcomes following ARET, considered patient selection is crucial, which requires a mechanistic understanding of individual ARET options. Here, we will discuss the differences between ARETs along with an overview of the current evidence base. We also outline future research priorities that will help refine the future role of ARET

The timed barium swallow and its relationship to symptoms in achalasia: Analysis of surface area and emptying rate

BACKGROUND: Timed barium swallow (TBS) is used to objectively measure response following achalasia therapy; however, findings can be discordant with symptoms. We hypothesized that measurement of surface area of the residual barium column would improve its utility in measuring outcome. METHODS: In a single-center cohort, achalasia patients undergoing therapy between September 2015-2016 who had TBS were included. Four metrics of emptying were studied: Post-therapy residual barium (a) absolute height and (b) surface area and percentage reduction in (c) residual height (%H) and (d) surface area (%SA) compared to pretherapy. Metrics were evaluated against symptom response (Eckardt score). KEY RESULTS: Twenty-four achalasics (median age 43 year; 13 males) were included; 14 received pneumatic dilatation, and 10 had peroral endoscopic myotomy. Treatment resulted in significant reduction in median Eckardt score (7 to 1; P = .03), mean residual barium column height (14.7 ± 8.7 to 7.9 ± 6.0 cm; P = .01) and surface area (52.7 ± 43.5 to 24.5 ± 23.6 cm2 ; P = .02). There were 4 (17%) initial non-responders (Eckardt > 3). % SA was best at discriminating between responders and non-responders (area under curve 0.85 ± 0.08; sensitivity 100%, specificity 80%). Concordance with symptomatic response following therapy was 83% when using 45% as the cutoff for surface area reduction compared to pretherapy. Eight patients whose static barium height was discordant with symptoms became concordant when % SA was used as a measure of response. CONCLUSIONS & INFERENCES: Change in barium surface area is a superior measure of esophageal emptying and better correlates with treatment response than the conventional 5-minute barium height in defining objective response to achalasia therapy

Rumination syndrome: Assessment of vagal tone during and after meals and during diaphragmatic breathing

Background: Pathophysiology of rumination syndrome (RS) is not well understood. Treatment with diaphragmatic breathing improves rumination syndrome. The aim of the study was to characterize vagal tone in patients with rumination syndrome during and after meals and during diaphragmatic breathing. Methods: We prospectively recruited 10 healthy volunteers (HV) and 10 patients with RS. Subjects underwent measurement of vagal tone using heart rate variability. Vagal tone was measured during baseline, test meal and intervention (diaphragmatic (DiaB), slow deep (SlowDB), and normal breathing). Vagal tone was assessed using mean values of root mean square of successive differences (RMSSD), and area under curves (AUC) were calculated for each period. We compared baseline RMSSD, the AUC and meal‐induced discomfort scores between HV and RS. Furthermore, we assessed the effect of respiratory exercises on symptom scores, and number of rumination episodes. Key Results: There was no significant difference in baseline vagal tone between HV and RS. During the postprandial period, there was a trend to higher vagal tone in RS, but not significantly (P > .2 for all). RS had the higher total symptom scores than HV (P < .011). In RS, only DiaB decreased the number of rumination episodes during the intervention period (P = .028), while both DiaB and SlowDB increased vagal tone (P < .05 for both). The symptom scores with the 3 breathing exercises showed very similar trends. Conclusions and inferences: Patients with RS do not have decreased vagal tone related to meals. DiaB reduced number of rumination events by a mechanism not related to changes in vagal tone

The treatment of achalasia patients with esophageal varices: an international study

Background: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. Methods: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. Results: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller’s myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p < 0.0001) at 6 months follow-up, with treatment outcomes resembling those of 20 non- cirrhotic achalasia patients who underwent similar therapy. No patients had recorded complications of bleeding or perforation. Conclusion: This study shows an excellent short-term symptomatic response in patients with esophageal achalasia and varices and demonstrates that the therapeutic outcomes and complications, other than transient encephalopathy in both patients who had a portosystemic shunt, did not differ to disease-matched patients without varices

The Clinical Relevance of Manometric Esophagogastric Junction Outflow Obstruction Can Be Determined Using Rapid Drink Challenge and Solid Swallows

INTRODUCTION: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO. METHODS: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated. RESULTS: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02). DISCUSSION: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol

The natural history of low-grade dysplasia in Barrett's esophagus and risk factors for progression

Background and Aim: Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma. The optimal management of low-grade dysplasia arising in Barrett's esophagus remains controversial. We performed a retrospective study from a tertiary referral center for Barrett's esophagus neoplasia, to estimate time to progression to high-grade dysplasia/esophageal adenocarcinoma in patients with confirmed low-grade dysplasia compared with those with downstaged low-grade dysplasia from index presentation and referral. We analyzed risk factors for progression. Methods: We analyzed consecutive patients with low-grade dysplasia in Barrett's esophagus referred to a single tertiary center (July 2006–October 2018). Biopsies were reviewed by at least two expert pathologists. Results: One hundred and forty-seven patients referred with suspected low-grade dysplasia were included. Forty-two of 133 (32%) of all external referrals had confirmed low-grade dysplasia after expert histopathology review. Multivariable analysis showed nodularity at index endoscopy (P < 0.05), location of dysplasia (P = 0.05), and endoscopic therapy after referral (P = 0.09) were associated with progression risk. At 5 years, 59% of patients with confirmed low-grade dysplasia had not progressed versus 74% of patients in the cohort downstaged to non-dysplastic Barrett's esophagus. Conclusion: Our data show variability in the diagnosis of low-grade dysplasia. The cumulative incidence of progression and time to progression varied across subgroups. Confirmed low-grade dysplasia had a shorter progression time compared with the downstaged group. Nodularity at index endoscopy and multifocal low-grade dysplasia were significant risk factors for progression. It is important to differentiate these high-risk subgroups so that decisions on surveillance/endotherapy can be personalized

Impaired motility in Barrett's esophagus: A study using high-resolution manometry with physiologic challenge

BACKGROUND: Esophageal dysmotility may predispose to Barrett's esophagus (BE). We hypothesized that high-resolution manometry (HRM) performed with additional physiologic challenge would better delineate dysmotility in BE. METHODS: Included patients had typical reflux symptoms and underwent endoscopy, HRM with single water swallows and adjunctive testing with solids and rapid drink challenge (RDC) before ambulatory pH-impedance monitoring. BE and endoscopy-negative reflux disease (ENRD) subjects were compared against functional heartburn patient-controls (FHC). Primary outcome was incidence of HRM contractile abnormalities with standard and adjunctive swallows. Secondary outcomes included clearance measures and symptom association on pH-impedance. KEY RESULTS: Seventy-eight patients (BE 25, ENRD 27, FHC 26) were included. Water swallow contractility was reduced in both BE (median DCI 87 mm Hg/cm/s) and ENRD (442 mm Hg/cm/s) compared to FHC (602 mm Hg/cm/s; P < .001 and .04, respectively). With the challenge of solid swallows and RDC, these parameters improved in ENRD (solids = 1732 mm Hg/cm/s), becoming similar to FHC (1242 mm Hg/cm/s; P = .93), whereas abnormalities persisted in BE (818 mm Hg/cm/s; P < .01 c.f. FHC). In BE and ENRD, reflux events (67 vs 57 events/24 hour) and symptom frequency were similar; yet symptom correlation was significantly better in ENRD compared to BE, which was comparable to FHC (symptom index 30% vs 4% vs 0%, respectively). Furthermore, bolus clearance and exposure times were more pronounced in BE (P < .01). CONCLUSIONS & INFERENCES: Reduced contractile effectiveness persisted in BE with the more representative esophageal challenge of swallowing solids and free drinking; while in ENRD and FHC peristalsis usually improved, demonstrating peristaltic reserve. Furthermore, symptom association and refluxate clearance were reduced in BE. These factors may underlie BE pathogenesis

Systematic assessment with I-SCAN magnification endoscopy and acetic acid improves dysplasia detection in patients with Barrett's esophagus

BACKGROUND AND STUDY AIMS: Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett's esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. METHODS: BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. RESULTS: The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a "pull-through" alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). CONCLUSIONS: A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785)