Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice. From a conventional pathophysiological perspective, GERD is conceptualized as ...incompetence of the antireflux barrier at the esophagogastric junction; the more severe that incompetence, the worse the disease. However, it is increasingly clear that many presentations of GERD represent distinct phenotypes with unique predisposing cofactors and pathophysiology outside of this paradigm. Three major consensus initiatives have grappled with this dilemma (the Montreal Consensus, The Rome Foundation, and the Lyon Consensus), each from a different perspective. Montreal struggled to define the disease, Rome sought to characterize its functional attributes, while Lyon examined its physiological attributes. Here, we merge the 3 perspectives, developing the concept that what has come to be known as GERD is actually a family of syndromes with a complex matrix of contributing pathophysiology. A corollary to this is that the concept of one size fits all to therapeutics does not apply, and that although escalating treatment with proton pump inhibitors (PPIs) may be pertinent to healing esophagitis, its applicability beyond that is highly questionable. Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, and visceral and central hypersensitivity on symptom severity has greatly oversimplified the problem. That oversimplification has led to excessive use of PPIs for everything captured under the GERD umbrella and shown a broad spectrum of syndromes less amenable to PPI therapy in any dose. It is with this in mind that we delineate this precision medicine concept of GERD.
Background
The contributions of swallowing and belching to specific gastroesophageal reflux disease (GERD) phenotypes are unclear.
Methods
This study retrospectively analyzed esophageal pH/impedance ...studies, comparing reflux events preceded by gastric belching (GB), supragastric belching (SGB), air swallowing, and liquid/solid swallowing based on reflux position, lower esophageal sphincter (LES) pressure, and acid exposure time (AET).
Key Results
20 GERD patients and 10 controls were studied. Upright GERD patients and controls had a higher proportion of reflux events with a preceding swallow or belch (0.64, 0.64) than the supine group (0.38, p = 0.043). The upright group and controls trended toward a higher proportion of reflux events preceded by overall swallowing (0.61, 0.50) and air swallowing (0.55, 0.48) than the supine group (0.32, 0.31 p = 0.064, p = 0.11), but the three groups had similar rates of liquid/solid swallowing (0.032, 0.024, 0.017, p = 0.69). LES pressure did not correlate with reflux events preceded by swallowing (R2 = 0.021, p = 0.44). There was a higher rate of events preceded by gastric belching in the control group (0.14) than in the upright (0.032) and supine groups (0.066, p = 0.049). LES pressure did not correlate with the rate of events preceded by belching (R2 = 0.000093, p = 0.96). Normal AET patients had a higher rate of events preceded by GB (0.12) than those with increased acid exposure (0.030, p = 0.0083), but the two groups had similar rates of preceding air (0.43, 0.47, p = 0.68), liquid/solid (0.018, 0.032, p = 0.30), and overall swallowing (0.44, 0.53, p = 0.38).
Conclusions and Inferences
Swallowing more than belching is a dominant mechanism for reflux irrespective of GERD position, LES pressure, and AET.
We retrospectively compared the rates of reflux events preceded by air swallowing, liquid/solid swallowing, gastric belching, and supragastric belching between patients with supine versus upright versus no GERD, and between patients with increased versus normal acid exposure. Swallowing more than belching was the dominant mechanism for reflux across all phenotypes.
Background & Aims Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled ...phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. Methods In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. Results At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively ( P < .05 for all). For BOS vs placebo, change in DSQ score was −14.3 vs −7.5 ( P = .0096), histologic response rates were 39% vs 3% ( P < .0001), and change in endoscopic severity score was −3.8 vs 0.4 ( P < .0001). Adverse events were similar between groups. Conclusions Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments. ClinicalTrials.gov ID NCT01642212.
Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ...'PPI-responsive oesophageal eosinophilia' (PPI-REE). PPI-REE refers to patients with clinical and histological features of EoE that remit with PPI treatment. Recent and evolving evidence, mostly from adults, shows that patients with PPI-REE and patients with EoE at baseline are clinically, endoscopically and histologically indistinguishable and have a significant overlap in terms of features of Th2 immune-mediated inflammation and gene expression. Furthermore, PPI therapy restores oesophageal mucosal integrity, reduces Th2 inflammation and reverses the abnormal gene expression signature in patients with PPI-REE, similar to the effects of topical steroids in patients with EoE. Additionally, recent series have reported that patients with EoE responsive to diet/topical steroids may also achieve remission on PPI therapy. This mounting evidence supports the concept that PPI-REE represents a continuum of the same immunological mechanisms that underlie EoE. Accordingly, it seems counterintuitive to differentiate PPI-REE from EoE based on a differential response to PPI therapy when their phenotypic, molecular, mechanistic and therapeutic features cannot be reliably distinguished. For patients with symptoms and histological features of EoE, it is reasonable to consider PPI therapy not as a diagnostic test, but as a therapeutic agent. Due to its safety profile, ease of administration and high response rates (up to 50%), PPI can be considered a first-line treatment before diet and topical steroids. The reasons why some patients with EoE respond to PPI, while others do not, remain to be elucidated.
Editorial: the CTA on EGIDs Jodorkovsky, Daniela; Katzka, David A.
Alimentary pharmacology & therapeutics,
July 2022, 2022-07-00, 20220701, Volume:
56, Issue:
2
Journal Article
Peer reviewed
LINKED CONTENT
This article is linked to Genta et al papers. To view these articles, visit https://doi.org/10.1111/apt.16971 and https://doi.org/10.1111/apt.17047
Current state of rumination syndrome Pomenti, Sydney; Katzka, David A
Diseases of the esophagus,
2024-May-13, 2024-05-13, 20240513
Journal Article
Peer reviewed
Rumination syndrome (RS) is an underdiagnosed behavioral disorder of recurrent regurgitation. Regurgitation occurs in RS due to increased gastric pressure achieved by subconscious contraction of the ...abdominal musculature wall, reversing the pressure gradient between the esophagus and the stomach. RS is mainly diagnosed clinically by the Rome Criteria with symptoms of regurgitation without retching of recently ingested food into the mouth and subsequent spitting or re-mastication. When the diagnosis is unable to be made clinically, supportive testing including fed impedance manometry can be considered. RS occurs worldwide, affecting patients of all ages, races, and genders with a prevalence of 3.1-5.8%. There is significant overlap with RS and disorders of a gut-brain interaction and upright gastroesophageal reflux driven by aerophagia and supragastric belching. There is also an association with mood disorder, fibromyalgia, and eating disorders. RS may be misdiagnosed as a variety of other syndromes including gastroesophageal reflux disease, gastroparesis, achalasia, and bulimia nervosa. Once RS is diagnosed, the mainstay of treatment is diaphragmatic breathing to lower the intragastric pressure and increase the lower esophageal pressure. Diaphragmatic breathing can be supported with biofeedback and cognitive behavioral therapy as well as medication options for more refractory cases. Response to therapy overtime and changes in symptoms overtime can now be tracked with a validated questionnaire.
Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (<50 years) patients with esophageal adenocarcinoma. We aimed to assess time trends in the ...incidence and outcomes of "young-onset" esophageal adenocarcinoma using a population-based database.
We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: <50, 50 to 69, and ≥70 years. Staging was stratified as localized, regional, and distant. Trends in incidence, disease stage, and survival were assessed in three periods (1975-89, 1990-99, and 2000-2015). Univariate and multivariate models were created to identify predictors of mortality.
Esophageal adenocarcinoma incidence has increased in patients <50 years of age, with an annual percentage change of 2.9% (95% confidence interval, 1.4%-4.4%) from 1975 to 2015. Young-onset esophageal adenocarcinoma presented at more advanced stages (regional + distant) compared with older patients (84.9% vs. 67.3%;
< 0.01), with increasing proportion of advanced stages over the study period. These patients also experienced poorer 5-year esophageal adenocarcinoma-free survival compared with older patients (22.9%% vs. 29.6%;
< 0.01), although this finding was attenuated on stage-stratified analysis.
Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma-free survival.
Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma-specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.
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