The natural history of gastro-esophageal reflux disease: a comprehensive review.

Gastroesophageal reflux disease (GERD) is a common disorder of the upper gastrointestinal tract which is typically characterized by heartburn and acid regurgitation. These symptoms are widespread in the community and range from 2.5% to more than 25%. Economic analyses showed an increase in direct and indirect costs related to the diagnosis, treatment and surveillance of GERD and its complications. The aim of this review is to provide current information regarding the natural history of GERD, taking into account the evolution of its definition and the worldwide gradual change of its epidemiology. Present knowledge shows that there are two main forms of GERD, that is erosive reflux disease (ERD) and non-erosive reflux disease (NERD) and the latter comprises the majority of patients (up to 70%). The major complication of GERD is the development of Barrett esophagus, which is considered as a pre-cancerous lesion. Although data from medical literature on the natural history of this disease are limited and mainly retrospective, they seem to indicate that both NERD and mild esophagitis tend to remain as such with time and the progression from NERD to ERD, from mild to severe ERD and from ERD to Barrett's esophagus may occur in a small proportion of patients, ranging from 0 to 30%, 10 to 22% and 1 to 13% of cases, respectively. It is necessary to stress that these data are strongly influenced by the use of powerful antisecretory drugs (PPIs). Further studies are needed to better elucidate this matter and overcome the present limitations represented by the lack of large prospective longitudinal investigations, absence of homogeneous definitions of the various forms of GERD, influence of different treatments, clear exclusion of patients with functional disorders of the esophagus.

The GerdQ questionnaire and high resolution manometry support the hypothesis that proton pump inhibitor-responsive oesophageal eosinophilia is a GERD-related phenomenon.

BACKGROUND: Little is known about the relationship between proton pump inhibitor-responsive oesophageal eosinophilia (PPI-REE), eosinophilic esophagitis (EoE) and gastro-oesophageal reflux disease (GERD). AIM: To compare high resolution manometry features and symptom profiles of patients with EoE, PPI-REE and GERD. METHODS: Consecutive patients diagnosed with EoE or PPI-REE according to international criteria (presence of at least one typical symptom of oesophageal dysfunction; at least 15 eosinophils per high-power field at mid/proximal oesophagus, persistence or resolution of eosinophils after an 8-week PPI trial), and a group of patients with proven GERD and oesophageal eosinophilia, prospectively completed the GerdQ questionnaire and underwent high resolution manometry. RESULTS: Thirty-five patients with EoE, 17 with PPI-REE and 27 with GERD were enrolled. When compared to GERD, both EoE and PPI-REE had higher rates of dysphagia (15% vs. 94% vs. 88%, P < 0.0001), patients with EoE reported heartburn and regurgitation less frequently (26% vs. 85%, and 17% vs. 74%, respectively; P < 0.001 for each and had lower GerdQ score [1 (0-6) vs. 8 (6-12), P < 0.001] than GERD patients. There was no significant difference comparing PPI-REE and GERD patients. Patients with PPI-REE had a higher prevalence of erosive oesophagitis than patients with EoE (35% vs. 9%, P = 0.04), which was similar to that of GERD (48%, P = 0.54). Patients with EoE had a lower frequency of high resolution manometry features associated with GERD than patients with PPI-REE. There was no significant difference between PPI-REE and GERD patients. CONCLUSION: GERD, as assessed by GerdQ and high resolution manometry is common in patients with PPI-REE, which may share similar pathogenic mechanisms.

Esophagogastric junction contractility for clinical assessment in patients with GERD: a real added value?

BACKGROUND: The role of esophagogastric junction contractile integral (EGJ-CI) as assessed by high-resolution manometry (HRM) is unclear. We aimed to correlate the EGJ-CI with impedance-pH findings in gastro-esophageal reflux disease (GERD) patients. METHODS: Consecutive patients with GERD symptoms were enrolled. All patients underwent upper endoscopy, HRM, and impedance-pH testing. The EGJ-CI was calculated using the distal contractile integral tool box during three consecutive respiratory cycles. The value was then divided by the duration of these cycles. A value below 13 was considered as a defective EGJ-CI. We also assessed EGJ morphology, esophageal acid exposure time (AET), number of reflux episodes (NRE), and symptom association analysis (SAA). A positive impedance-pH monitoring was considered in case of abnormal AET and/or NRE and/or positive SAA. KEY RESULTS: Among 130 patients we enrolled, 91 had GERD (abnormal AET and/or elevated NRE and/or positive SAA) and 39 had functional heartburn (FH) (negative endoscopy, normal AET, normal NRE, and negative SAA). The GERD patients had a lower median value of EGJ-CI (11 [3.1-20.7] vs 22 [9.9-41], p < 0.02) compared to FH patients. Patients with a defective EGJ-CI had, more frequently, a positive impedance-pH monitoring or esophageal mucosal lesions at endoscopy (p < 0.05 and p < 0.05, respectively) than patients with a normal EGJ-CI. An EGJ-CI cut-off value of 5 mmHg cm yielded the optimal performance in identifying GERD at impedance-pH (sensitivity 89%-specificity 63%). CONCLUSIONS & INFERENCES: A defective EGJ-CI at HRM is clearly associated with evidence of GERD at impedance-pH monitoring. Evaluating EGJ-CI may be useful to predict an abnormal impedance-pH testing.

Esophagogastric junction morphology is associated with a positive impedance-pH monitoring in patients with GERD.

BACKGROUND: High-resolution manometry (HRM) provides information on esophagogastric junction (EGJ) morphology, distinguishing three different subtypes. Data on the correlation between EGJ subtypes and impedance-pH detected reflux patterns are lacking. We aimed to correlate the EGJ subtypes with impedance-pH findings in patients with reflux symptoms. METHODS: Consecutive patients with suspected gastroesophageal reflux disease (GERD) were enrolled. All patients underwent HRM and impedance-pH testing off-therapy. EGJ was classified as: Type I, no separation between the lower esophageal sphincter (LES) and crural diaphragm (CD); Type II, minimal separation (>1 and <2 cm); Type III, ≥ 2 cm separation. We measured esophageal acid exposure time (AET), number of total reflux episodes and symptom association analysis. KEY RESULTS: We enrolled 130 consecutive patients and identified 46.2% Type I EGJ, 38.5% Type II, and 15.4% Type III patients. Type III subjects had a higher number of reflux episodes (61 vs 45, p < 0.03, vs 25, p < 0.001), a greater mean AET (12.4 vs 4.2, p < 0.02, vs 1.5, p < 0.001) and a greater positive symptom association (75% vs 72%, p = 0.732 vs 43.3%, p < 0.02) compared with Type II and I patients, respectively. Furthermore, Type II subjects showed statistically significant (overall p < 0.01) increased reflux when compared with Type I patients. Type III and II EGJ morphologies had a more frequent probability to show a positive multichannel intraluminal impedance pH monitoring than Type I (95% vs 84% vs 50%, p < 0.001). CONCLUSIONS & INFERENCES: Increasing separation between LES and CD can cause a gradual and significant increase in reflux. EGJ morphology may be useful to estimate an abnormal impedance-pH testing in GERD patients.