24-h impedance-pH Monitoring Research Articles

Mo1913 Reflux Associated With Symptoms: Does the Impedance Pattern Matter?

Introduction Different phenotypes of GERD-suspected patients who do not respond to proton pump inhibitor (PPI) therapy might be identified using pH-impedance monitoring. Our aim was to describe demographic, manometric and impedance patterns associated with phenotypes of PPI non-responders. Patients and methods PPI non-responders (without previous foregut surgery, scleroderma or achalasia) referred for 24-h esophageal pH-impedance monitoring on PPI were recruited. Demographic data, results of upper GI endoscopy and high resolution manometry were collected. Two investigators reviewed pH-impedance studies; a 3rd one arbitrated disagreements. Based on impedance pattern, reflux events were characterized as belch, supragastric belch, reflux starting with belch, reflux induced by supragastric belch, reflux associated with belch, reflux associated with supragastric belch, proximal liquid reflux, swallow-induced reflux, distal liquid reflux. Patients were classified into 3 groups: persistent acid reflux (acid esophageal exposure time (AET; esophageal pH 5% of total time), reflux sensitive esophagus (AET<5%, symptom index (SI)≥50%), and functional heartburn (AET<5%, SI<50%, absence of Barrett's esophagus). Data are presented as percentage or median (range) and compared using Chi2 or Mann Whitney test. Results Eighty PPI non-responders (30 males, mean age 51 years (range 19-76), mean body mass index (BMI) 29.5 kg/m2 (range 18.6-44.1)) were included. AET was 0.5% (0.0-35.5) of total time and median number of reflux events (liquid, gas or mixed) was 45 (4-221). Eight patients (10%) had persistent acid reflux, 29 (36.2%) reflux sensitive esophagus and 43 (53.8%) functional heartburn. Characteristics of these groups are described in Table 1. Patients with persistent acid reflux had less frequently normal esophageal motility than the other patients groups (29% vs 46%, p<0.01). Patients with reflux sensitive esophagus or functional heartburn tended to present more frequently supra-gastric belch than patients with persistent acid reflux (60% vs 25, p=0.067). Distribution of dominant impedance patterns is presented in the Table 2. Conclusions The mechanistic reflux profile in PPI non-responders is heterogeneous. Although liquid reflux events were the most common mechanism of reflux in all three PPI non-responder subtypes, patients with reflux sensitivity and functional heartburn had much more variability in their mechanistic profile with a large proportion being associated with both suband supra-gastric belching. These different mechanistic profiles may have clinical implications as therapy targeting the dominant mechanism in each patient may be more effective. Table 1

Mo1120 The First 30-min Basal Impedance Levels Highly Correlate With the 24-Hour Values and Lower Values Are Associated With a Positive 24-h Impedance-pH Monitoring

Objectives: Recent data indicate that low esophageal baseline impedance (BI) measurements may reflect the status of the esophageal mucosa. We aimed to correlate the first 30-min baseline impedance (BI) levels with the 24-h BI values in patients with heartburn and negative endoscopy. Moreover, we correlated those values with the results of 24-h impedancepH.Methods: Sixty patients with heartburn and negative endoscopy underwent 24-h impedance-pH testing off-therapy and were sub-categorized in: a) patients with abnormal acid exposure time (AET) and/or number of refluxes (NERD); b) patients with pathophysiological characteristics related to functional heartburn (FH). Impedance-pH tracks were manually evaluated to assess the mean 24-h BI (15-min time window for each hour, avoiding refluxes and swallowing) and the first 30-min BI after the placement of the probe. Moreover, AET, number of refluxes and symptom/reflux correlation (SAP) were measured. Results: NERD showed a higher mean AET (6.3±1.6% vs 0.6±0.3%, p<0.05) and reflux number (78.1±23 vs 15.4±9.8, p<0.05) compared to FH. FH had a 100% negative SAP. The first 30-min BI was lower in NERD (1126.9±144.5) than in FH (3867.5±486.8) (p<0.001). There were no differences between the 24-h BI and the 30-min BI in both groups (1126.9±144.5 vs 1101±215.4 in NERD and 3867.5±486.8 vs. 3624.4±347.5 in FH; p=n.s.). We found a strong inverse correlation between BI (24-h and 30-min) and AET or total number of reflux events (see Figure 1). Conclusions: The 30-min BI levels directly correlate with 24-h BI and inversely correlate with AET. Moreover, the 30-min BI levels appear much lower in patients with a diagnosis of NERD at impedance-pH testing.

The effect of endoscopic fundoplication and proton pump inhibitors on baseline impedance and heartburn severity in GERD patients.

Antireflux therapy may lead to recovery of impaired mucosal integrity in gastro-esophageal reflux disease (GERD) patients as reflected by an increase in baseline impedance. The study objective was to evaluate the effect of endoscopic fundoplication and proton pump inhibitor (PPI) PPI therapy on baseline impedance and heartburn severity in GERD patients. Forty-seven GERD patients randomized to endoscopic fundoplication (n=32) or PPI therapy (n=15), and 29 healthy controls were included. Before randomization and 6months after treatment, baseline impedance was obtained during 24-h pH-impedance monitoring. Heartburn severity was evaluated using the GERD-HRQL questionnaire. Before treatment, baseline impedance in GERD patients was lower than in healthy controls (p<0.001). Antireflux therapy increased baseline impedance (from 1498 [IQR 951-2472] to 2393 [IQR 1353-3027] Ω, p=0.001), however it only led to a partial recovery when compared to healthy controls (2393 [IQR 1353-3027] vs 2983 [2335-3810] Ω, p<0.01). The effect of both treatment options was not significantly different (p=0.13) despite the increased number of non-acid reflux events in the PPI group. No correlation was found between baseline impedance and GERD symptoms before or after treatment. Reduction in acid reflux by endoscopic fundoplication or PPI therapy leads to an increase in baseline impedance in GERD patients, likely to reflect recovery of mucosal integrity. The impact of non-acid reflux events on esophageal mucosal integrity may be limited as no difference in the increase in baseline impedance was observed after both treatment options. The lack of association between impedance baseline and heartburn severity indicates that other factors may contribute to heartburn perception in GERD.

The diagnosis of gastro-esophageal reflux disease cannot be made with barium esophagograms.

For over 50years, barium studies have been used to diagnose gastro-esophageal reflux disease (GERD), but the value of this test is controversial. Our study aimed to determine if barium esophagograms can be used to diagnose GERD. Barium esophagograms and pH-impedance measurement were performed in 20 subjects with reflux symptoms. pH-impedance measurements were used as gold standard for the diagnosis of GERD. Gastro-esophageal reflux measured with the barium study was defined as a positive outcome. 50% of patients presented gastro-esophageal reflux on the barium esophagogram. No significant differences were observed in acid exposure time between subjects with (median: 7.4%; interquartile range, IQR: 8.4%) or without reflux at barium esophagography (median: 5.95%; IQR: 13.05%; p>0.05). Nor did we find differences in median proximal extent of reflux measured with impedance monitoring between patients with a positive (median: 6.7%; IQR: 1.95%) and negative barium study (median: 7.1%; IQR: 0.68%; p>0.05). Patients with reflux on barium esophagogram did not have a positive symptom association probability more often than those who did not have reflux at barium esophagography. Lastly, there were no differences in numbers of acid, weakly acidic or total reflux episodes between those with positive or negative barium esophagogram (p>0.05). No correlations were found between the maximum proximal extent of gastro-esophageal reflux during esophagography and pH-impedance parameters. Presence or absence of gastro-esophageal reflux during barium esophagography does not correlate with incidence or extent of reflux observed during 24-h pH-impedance monitoring and is not of value for the diagnosis of GERD.

Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects.

The 5-HT4 receptor agonist prucalopride is a prokinetic drug which improves colonic motility. Animal data and in vitro studies suggest that prucalopride also affects gastric and esophageal motor function. We aimed to assess the effect of prucalopride on gastric emptying, esophageal motility, and gastro-esophageal reflux in man. In this double-blind, placebo-controlled, randomized, crossover study, we included 21 healthy volunteers who received 4mg prucalopride or placebo per day for 6days. We performed high-resolution manometry (HRM) followed by 120-min HRM-pH-impedance monitoring after a standardized meal, ambulatory 24-h pH-impedance monitoring, and gastric emptying for solids. Prucalopride decreased (median [IQR]) total acid exposure time (3.4 [2.5-5.6] vs 1.7 [0.8-3.5] %, p<0.05). The total number of reflux events was unaffected by prucalopride, however, the number of reflux events extending to the proximal esophagus was reduced by prucalopride (15.5 [9.8-25.5] vs 10.5 [5.3-17.5], p<0.05). Furthermore, prucalopride improved acid clearance time (77.5 [47.8-108.8] vs 44.0 [30.0-67.8] s, p<0.05). Prucalopride did not affect the number of transient lower esophageal sphincter (LES) relaxations or their association with reflux events. Esophageal motility and basal pressure of the LES were not affected by prucalopride. Prucalopride increased gastric emptying (T1/2 ; 32.7 [27.9-44.6] vs 49.8 [37.7-55.0] min, p<0.05) and decreased residue after 120min (8.8 [4.4-14.8] vs 2.7 [1.3-5.4] %, p<0.05). Prucalopride reduces esophageal acid exposure and accelerates gastric emptying in healthy male volunteers. These findings suggest that the drug could be effective for treatment of patients with reflux disease and functional dyspepsia.

Accuracy of diagnosing gastroesophageal reflux disease by GerdQ, esophageal impedance monitoring and histology

To assess the performance of self-assessment gastroesophageal reflux disease questionnaire (GerdQ), 24-h impedance monitoring, proton pump inhibitor (PPI) test and intercellular space of esophageal mucosal epithelial cells in the diagnosis of gastroesophageal reflux disease (GERD). Patients with symptoms suspected of GERD were administered the GerdQ and underwent endoscopy (measurement of intercellular space in the biopsy specimen sampling at 2 cm above the Z-line) and 24-h impedance pH monitoring, together with a 2-week experimental treatment with esomeprazole. A total of 636 patients were included for the final analysis, including 352 with GERD. The sensitivity and specificity of GerdQ and 24-h impedance monitoring for diagnosing GERD were 57.7% and 48.9%, and 66.4% and 43.3%, respectively. The sensitivity of 24-h impedance pH monitoring increased to 93.7%. The sensitivity and specificity of dilated intercellular spaces (DIS) (≥0.9 μm) for diagnosing GERD were 61.2% and 56.1%, respectively, whereas those for PPI test were 70.5% and 44.4%. GerdQ score or PPI test alone cannot accurately diagnose GERD in a Chinese population suspected of GERD. A definitive diagnosis of GERD still depends on endoscopy or 24-h pH monitoring. 24-h impedance pH monitoring may increase the sensitivity for diagnosing GERD by 20%; however, when used alone, it results in poor specificity in patients without acid suppressive therapy.

Heterogeneity of mucosal mast cell infiltration in subgroups of patients with esophageal chest pain

Although there is growing evidence that an increase in mucosal mast cells (MMCs) in the small and large intestine is associated with visceral hypersensitivity, few studies have evaluated MMCs in humans with esophageal symptoms. The aim of this study was to investigate esophageal MMC distribution in patients with non-cardiac chest pain (NCCP) and to examine the association between the number of gut MMCs and other functional gastrointestinal disorders. Forty-two consecutive NCCP patients and 10 healthy controls completed a questionnaire for bowel symptoms, chest pain intensity score, and psychologic depression. Esophageal, duodenal, and rectal MMCs were identified immunohistochemically and quantified by image analysis. Numbers of MMCs were significantly higher in NCCP patients vs healthy controls (11.8±5.6 vs 7.6±3.7 MMCs/high-power field, p=0.026). In comparison of subgroups classified by 24-h impedance-pH monitoring, esophageal MMC counts were highest in the hypersensitive esophagus group (p<0.01) and were also significantly increased in the functional chest pain group (p<0.05). A positive correlation between esophageal and duodenal MMC counts was observed in patients with functional dyspepsia (FD; Spearman ρ=0.604, p=0.037). In particular, patients with clinical overlap with irritable bowel syndrome showed a strong positive correlation between esophageal and rectal MMC numbers (Spearman ρ=0.857, p=0.010). Among NCCP patients, increased MMC infiltration occurs in subgroups with hypersensitive esophagus and functional chest pain. In subpopulations with overlap with FD or irritable bowel syndrome, esophageal MMC counts demonstrated significant positive correlations with duodenal or rectal MMC counts.

Dysmotility and reflux disease

In the last decade, with the advent of new oesophageal testing [i.e. 24-h impedance-pH monitoring, combined impedance-manometry, high-resolution manometry (HRM)], relevant progress in understanding the mechanisms contributing to the development of gastro-oesophageal reflux disease (GORD) has been made, allowing a better management of patients with this disorder. The aim of our review is to report the state-of-the-art about oesophageal motor disorders in patients with reflux disease and to stimulate new research in this field. Hypotensive lower oesophageal sphincter (LOS), transient LOS relaxations, impairment of oesophagogastric junction including hiatal hernia, oesophageal bolus transit abnormalities and presence of ineffective oesophageal motility have been strongly implicated in GORD development. In particular, the majority of recent studies carried out with HRM and impedance-pH testing reported that these motor abnormalities are increasingly prevalent with increasing severity of GORD, from nonerosive reflux disease and erosive oesophagitis to Barrett's oesophagus. Defining and characterizing oesophageal dysmotility in patients with reflux disease is of maximum importance in order to properly diagnose these patients and to treat them with the best management of care. New studies are needed in order to better understand the physiomechanic basis of oesophageal dysmotility in GORD patients.

Refractory GERD

To compare the incidence of persistent abnormal acid exposure, hypersensitive esophagus (HE), and functional heartburn (FH) in obese/overweight and normal-weight patients referred for impedance-pH monitoring, because of persisting gastroesophageal reflux disease (GERD) symptoms despite therapy with proton pump inhibitors (PPIs). ΜETHODS: Patients with normal endoscopy and typical GERD symptoms, despite PPI therapy twice daily, underwent 24-h impedance-pH monitoring while on therapy. Distal esophageal acid exposure (% time pH<4) was measured and reflux episodes were classified into acid or nonacid. A positive symptom index was defined when at least 50% of symptom events were preceded by reflux episodes. Patients were categorized as those with persistent abnormal acid exposure, those with HE, and those with FH. The incidence of persistent abnormal acid exposure, HE, and FH between overweight/obese patients (BMI≥25 kg/m) and normal-weight patients (BMI<25 kg/m) was subsequently evaluated. A total of 246 patients (women: 158, men: 88, increased BMI: 151, normal BMI: 95, mean age 55, range 18-75 years) were included. Persistent abnormal acid exposure was found in 39 patients (increased BMI: 31, normal BMI: 8), HE in 77 patients (increased BMI: 43, normal BMI: 34), and FH in 118 patients (increased BMI: 69, normal BMI: 49). When comparing BMI among all three groups, patients with increased BMI were more likely to have acid reflux than HE or FH (P=0.03). In patients with GERD symptoms refractory to double-dose PPI therapy, those with increased BMI are more likely to have persistent abnormal acid exposure than HE or FH.

Weak Peristalsis With Large Breaks Is Associated With Higher Acid Exposure and Delayed Reflux Clearance in the Supine Position in GERD Patients

Ineffective esophageal motility is frequently observed in gastroesophageal reflux disease (GERD) patients but its clinical relevance remains controversial. In healthy subjects and in patients with nonobstructive dysphagia, it has been demonstrated, by means of high-resolution manometry (HRM), that long breaks of esophageal peristalsis predict delayed bolus clearance. HRM and 24-h multichannel impedance-pH (MI-pH) monitoring were performed in 40 GERD patients with no evidence of hiatal hernia. Total bolus clearing time (BCT) in upright and supine position and acid exposure time (AET) were calculated. Of the 40 patients, 23 showed a pathological AET and 15 erosive reflux disease (ERD). Patients with a pathological number of large breaks were characterized by a significantly lower BCT value in the supine position and higher AET. In all, 10/15 ERD patients (67%) and 5/25 nonerosive reflux disease patients (20%) were characterized by an abnormal number of small or large breaks (P<0.05). ERD patients were characterized by significantly higher AET and BCT in the supine position. GERD patients with a pathological number of large breaks, assessed by HRM, are characterized by a significantly prolonged reflux clearance in the supine position and higher AET. ERD patients display a higher number of esophageal breaks that might explain the development of erosions.

Effect of transoral incisionless fundoplication on reflux mechanisms

Transoral incisionless fundoplication (TIF) is a new endoscopic treatment option for gastroesophageal reflux disease (GERD). The mechanisms underlying the anti-reflux effect of this new procedure have not been studied. We therefore conducted this explorative study to evaluate the effect of TIF on reflux mechanisms, focusing on transient lower esophageal sphincter relaxations (TLESRs) and esophagogastric junction (EGJ) distensibility. GERD patients (N = 15; 11 males, mean age 41 years, range 23-66), dissatisfied with medical treatment were studied before and 6 months after TIF. We performed 90-min postprandial combined high-resolution manometry and impedance-pH monitoring and an ambulatory 24-h pH-impedance monitoring. EGJ distensibility was evaluated using an endoscopic functional luminal imaging probe before and directly after the procedure. TIF reduced the number of postprandial TLESRs (16.8 ± 1.5 vs. 9.2 ± 1.3; p < 0.01) and the number of postprandial TLESRs associated with reflux (11.1 ± 1.6 vs. 5.6 ± 0.6; p < 0.01), but the proportion of TLESRs associated with reflux was unaltered (67.6 ± 6.9 vs. 69.9 ± 6.3 %). TIF also led to a decrease in the number and proximal extent of reflux episodes and an improvement of acid exposure in the upright position; conversely, TIF had no effect on the number of gas reflux episodes. EGJ distensibility was reduced after the procedure (2.4 ± 0.3 vs. 1.6 ± 0.2 mm(2)/mmHg; p < 0.05). TIF reduced the number of postprandial TLESRs, the number of TLESRs associated with reflux and EGJ distensibility. This resulted in a reduction of the number and proximal extent of reflux episodes and improvement of acid exposure in the upright position. The anti-reflux effect of TIF showed to be selective for liquid-containing reflux only, thereby preserving the ability of venting gastric air.

Oesophageal baseline impedance values are decreased in patients with eosinophilic oesophagitis.

Gastro-oesophageal reflux has been suggested to play a role in eosinophilic oesophagitis (EoO). Oesophageal acid exposure decreases baseline intraluminal impedance, a marker of mucosal integrity, in patients with gastro-oesophageal reflux disease (GORD). The aim of this study was to assess oesophageal baseline impedance levels in EoO patients and to investigate their relationship with oesophageal acid exposure. Ambulatory 24-h pH-impedance monitoring was performed in 11 EoO patients and in 11 healthy controls with matched oesophageal acid exposure. We assessed baseline impedance levels in the distal, mid-, and proximal oesophageal impedance channels. BASELINE IMPEDANCE LEVELS IN EOO PATIENTS WERE MARKEDLY LOWER COMPARED TO CONTROLS IN THE DISTAL OESOPHAGUS (MEDIAN (INTERQUARTILE RANGE): 988 (757-1978) vs. 2259 (1767-2896) Ω, p = 0.015), mid-oesophagus (1420 (836-2164) vs. 2614 (2374-3879) Ω, p = 0.003), and proximal oesophagus (1856 (1006-2625) vs. 2868 (2397-3439) Ω, p = 0.005). Whereas baseline impedance decreased from proximal to distal in healthy subjects (p = 0.037), no such gradient was seen in EoO patients (p = 0.123). Throughout the oesophagus, baseline impedance values are decreased in EoO patients, indicating impaired mucosal integrity. Our findings suggest that factors other than acid reflux are the cause of low baseline impedance in EoO.

Gastroözofageal Reflü Hastalığı Tedavisinde Konvansiyonel Aletler ile Tek Kesi Laparoskopik Nissen Fundoplikasyon

Objective: Since the early 1990s with the development of minimally invasive techniques, laparoscopic Nissen fundoplication has become the gold standard intervention for the surgical treatment of gastroesophageal reflux disease (GERD), and antireflux surgical treatment of GERD can be performed by the single incision laparoscopic technique. In this study, we aimed to assess the safety and feasibility of single incision laparoscopic Nissen fundoplication (SILNF) with a new liver retraction technique. Material and Methods: Ten patients underwent single incision laparoscopic Nissen fundoplication between October 2011 and March 2012. In all patients, upper gastrointestinal endoscopy was performed. Ambulatory 24-h pH impedance monitoring was performed in all patients. The skin, subcutaneous tissue and fascia were incised with a 20 mm vertical midline incision above the umbilicus, and a SILS-Port TM (Covidien Corp, Mansfield, MA, USA) was placed with conventional laparoscopic hand instruments. Results: The procedure was successfully performed in all ten patients. The mean Johnson-DeMeester score was 29±7.9. The mean operation time was 93±14.1 minutes. The hiatal area was clearly visible with the new liver retraction technique which was applied in this study. None of the patients required conversion to an open procedure. Two patients required the insertion of an additional port. There were no intraoperative or early postoperative complications. Conclusion: SILNF is safe and technically feasible, and it can be performed with conventional laparoscopic instruments.

Direct Measurement of Gastroesophageal Reflux Episodes in Patients With Squamous Cell Carcinoma by 24-h pH-Impedance Monitoring

Recent studies have consistently reported a significant association between gastric atrophy and esophageal squamous cell carcinomas (ESCCs). However, causative factors responsible for the linkage remain to be clarified. Multichannel intraluminal impedance monitoring in conjunction with a pH sensor (MII-pH) is a reliable technique to evaluate gastroesophageal reflux (GER) episodes, independent of the acidity. We investigated the potential roles of GER in the pathogenesis of ESCC with MII-pH. From August 2008 to May 2010, 14 consecutive inpatients with superficial ESCCs (ESCC group) and 14 age- and sex-matched inpatients without any esophageal dysplastic lesions (non-ESCC group) were enrolled. Twenty-four hour portable MII-pH monitoring was performed under standard hospitalized conditions. The data of MII-pH were used to identify acid reflux (AR: pH drop below 4.0 during a reflux episode) and non-AR (NAR: pH drop above 4.0 during a reflux episode). The median intragastric pH of the ESCC group was 4.7 (2.3-6.4), implying hypochlorhydria in this patient group. The numbers of total reflux and NAR episodes in the ESCC group were significantly higher than those in the non-ESCC group (56 (43-87) vs. 35.5 (18-47), P=0.016 for total reflux and 46.5 (32-84) vs. 24.5 (8-37), P=0.012 for NAR), whereas the numbers of AR were similar in both groups. In addition, there was significance in the category of percentage time of bolus reflux episodes. Using MII-pH monitoring, we revealed the clinical significance of GER, especially NAR, in ESCCs. NAR may be a key factor in the link between gastric atrophy and ESCCs.

Esophageal Acid Exposure Decreases Intraluminal Baseline Impedance Levels

Intraluminal baseline impedance levels are determined by the conductivity of the esophageal wall and can be decreased in gastroesophageal reflux disease (GERD) patients. The aim of this study was to investigate the baseline impedance in GERD patients, on and off proton pump inhibitor (PPI), and in healthy controls. Ambulatory 24-h pH-impedance monitoring was performed in (i) 24 GERD patients with and 24 without pathological esophageal acid exposure as well as in 10 healthy controls and in (ii) 20 patients with refractory GERD symptoms despite PPI, once on PPI and once off PPI. Baseline impedance levels in the most distal and the most proximal impedance channels were assessed. Median (interquartile range) distal baseline impedance in patients with physiological (2,090 (1,537-2,547) Ω) and pathological (781 (612-1,137) Ω) acid exposure was lower than in controls (2,827 (2,127-3,270) Ω, P<0.05 and P<0.001). A negative correlation between 24-h acid exposure time and baseline impedance was observed (r=-0.7, P<0.001). In patients measured off and on PPI, median distal baseline impedance off PPI was significantly lower than on PPI (886 (716-1,354) vs. 1,372 (961-1,955) Ω, P<0.05) and distal baseline impedance in these groups was significantly lower than in healthy controls (P<0.05 and P<0.001). Proximal baseline impedance did not differ significantly between the patients off PPI and on PPI (1,793 (1,384-2,489) vs. 1,893 (1,610-2,561) Ω); however, baseline impedance values in both measurements were significantly lower than in healthy controls (3,648 (2,815-3,932) Ω, both P<0.001). These findings suggest that baseline impedance is related to esophageal acid exposure and could be a marker of reflux-induced changes to the esophageal mucosa.

The Relevance of Reflux Monitoring Off Therapy

To the Editor: We read the recent article by Vaezi (1). with interest. The author discussed on the opportunity to evaluate patients with symptoms suggestive of gastro-esophageal reflux by means of 24-h pH or impedance-pH monitoring On or Off therapy. He concluded that, after an empiric trial with twice-daily proton pump inhibitors (PPIs) therapy, in case of refractoriness, patients should undergo reflux monitoring On therapy in order to exclude reflux disease, while testing Off therapy has a limited value, because in this group it results only in an additional test proving what is already established by patients' lack of response to aggressive PPI therapy.

Selective Serotonin Reuptake Inhibitors for the Treatment of Hypersensitive Esophagus: A Randomized, Double-Blind, Placebo-Controlled Study

Ambulatory 24-h pH-impedance monitoring can be used to assess the relationship of persistent symptoms and reflux episodes, despite proton pump inhibitor (PPI) therapy. Using this technique, we aimed to identify patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on their symptoms. Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, and regurgitation), despite PPI therapy twice daily, underwent 24-h pH-impedance monitoring. Distal esophageal acid exposure (% time pH <4) was measured and reflux episodes were classified into acid or non-acid. A positive symptom index (SI) was declared if at least half of the symptom events were preceded by reflux episodes. Patients with a normal distal esophageal acid exposure time, but with a positive SI were classified as having hypersensitive esophagus and were randomized to receive citalopram 20 mg or placebo once daily for 6 months. A total of 252 patients (150 females (59.5%); mean age 55 (range 18-75) years) underwent 24-h pH-impedance monitoring. Two hundred and nineteen patients (86.9%) recorded symptoms during the study day, while 105 (47.9%) of those had a positive SI (22 (20.95%) with acid, 5 (4.76%) with both acid and non-acid, and 78 (74.29%) with non-acid reflux). Among those 105 patients, 75 (71.4%) had normal distal esophageal acid exposure time and were randomized to receive citalopram 20 mg (group A, n=39) or placebo (group B, n=36). At the end of the follow-up period, 15 out of the 39 patients of group A (38.5%) and 24 out of the 36 patients of group B (66.7%) continue to report reflux symptoms (P=0.021). Treatment with SSRIs is effective in a select group of patients with hypersensitive esophagus.

Diagnostic values of GerdQ, 24-h ambulatory oesophageal pH and impedance-pH monitoring in Barrett's esophagus, reflux esophagitis and non-erosive reflux disease

To compare the diagnostic values of GerdQ questionnaire, 24-h pH monitoring and 24-h impedance-pH monitoring for gastroesophageal reflux disease (GERD) and to analyze the reflux patterns of Barrett's esophagus (BE), reflux esophagitis (RE) and non-erosive disease (NERD). From June 1, 2009 to September 30, 2010, 205 GERD patients were included according to the Montreal consensus. All were surveyed by a GerdQ questionnaire and underwent 24-h impedance-pH monitoring. The diagnostic sensitivities of GerdQ, 24-h pH-DeM and 24-h IMP-pH were compared and the reflux pattern of BE, RE and NERD analyzed. A total of 205 GERD patients including 10 BE, 28 RE and 167 NERD were recruited. (1) The diagnostic rate of 24-h IMP-pH was 74.1%. It was significantly higher than that of GerdQ (51.7%) and 24-h pH-DeM (29.2%). (2) The diagnostic sensitivities of GerdQ and 24-h pH-DeM for BE and RE were higher than that for NERD. But there were no significant differences of 24-h IMP-pH for three types of GERD (70.0%, 82.1% and 73.1%). (3) There were positive correlations among the scores of GerdQ, pH-DeM scores and acid scores in IMP-pH (r = 0.242, P = 0.000; r = 0.182, P = 0.009 and r = 0.632, P = 0.000). (4) Added diagnostic values of IMP-pH were 58.5% and 74.5% respectively in patients who would have been missed by GerdQ and pH-DeM. (5) The detection rate and score of acid reflux in RE patients were higher than that of NERD [53.6% vs 23.4%, P < 0.05; 45.6 (35.0 - 67.5) vs 23.1 (9.3 - 35.0), P < 0.05]. But gas score and separate acid reflux were lower than that in NERD [17 (0 - 194) vs 30 (0 - 500), P < 0.05; 57.4% vs 28.6%, P < 0.05]. Acid reflux plays an important role in RE. The value of GerdQ and 24-h pH-DeM and 24-h IMP-pH monitoring were similar for the diagnosis of RE. Weak acid may be more important for BE and NERD patients than separate acid reflux. And 24-h IMP-pH monitoring has a distinct advantage in diagnosing these two types.

Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease

ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects. To evaluate the effects of ADX10059 monotherapy for 2 weeks on symptom control in patients with GERD. This was a double-blind, placebo-controlled, multi-centre trial in GERD patients who were responders to proton pump inhibitors (PPIs). Following PPIs withdrawal, a 2-week baseline washout period was followed by 2-week treatment with either ADX10059 120 mg or placebo b.d. The primary clinical efficacy endpoint was the number of GERD symptom-free days in treatment week 2 compared with the last 7 days of baseline. The effect on reflux events using 24-h impedance-pH monitoring was also determined in a subset of 24 patients. The full analysis set comprised 103 patients ADX10059 (N= 50), Placebo (N=53). In treatment week 2, ADX10059 significantly increased GERD symptom-free days (P=0.045) and heartburn-free days (P=0.037), reduced antacid use (P=0.017), improved total symptom score (P=0.048) including subscale heartburn/regurgitation (P=0.007) and sleep disturbance because of GERD (P= 0.022). ADX10059 significantly reduced total (P=0.034) and acidic reflux events (P=0.003). ADX10059 was well tolerated. Most common adverse events for ADX10059 were mild to moderate dizziness 16% and vertigo 12% (placebo 4% and 2%). Inhibition of mGluR5 with ADX10059 monotherapy reduces reflux events and improves symptoms in GERD patients. This mechanism has promise for the management of GERD.

Effects of anti-reflux surgery on weakly acidic reflux and belching

BackgroundLaparoscopic Nissen fundoplication (LNF) is the most frequently performed operation for gastro-oesophageal reflux disease (GORD). However, 12% of the patients have persistent reflux symptoms and 19% develop gas-related symptoms after...