Radu Tutuian

Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy. A multicentre study using combined ambulatory impedance-pH monitoring

Background and aims: Empiric proton pump inhibitor (PPI) trials have become increasingly popular leading to gastroenterologists frequently evaluating gastro-oesophageal reflux disease (GORD) patients only after they have “failed” PPI therapy. Combined multichannel intraluminal impedance and pH (MII-pH) monitoring has the ability to detect gastro-oesophageal reflux (GOR) episodes independent of their pH and evaluate the relationship between symptoms and all types of GOR. Using this technique, we aimed to characterise the frequency of acid and non-acid reflux (NAR) and their relationship to typical and atypical GOR symptoms in patients on PPI therapy. Methods: Patients with persistent GORD symptoms referred to three centres underwent 24 hour combined MII-pH monitoring while taking PPIs at least twice daily. Reflux episodes were detected by impedance channels located 3, 5, 7, 9, 15, and 17 cm above the lower oesophageal sphincter (LOS) and classified into acid or non-acid based on pH data from 5 cm above the LOS. A positive symptom index (SI) was declared if at least half of each specific symptom events were preceded by reflux episodes within five minutes. Results: A total of 168 patients (103 (61%) females and 65 (39%) males; mean age 53 (range 18–85) years) underwent combined MII-pH monitoring while taking PPIs at least twice daily. One hundred and forty four (86%) patients recorded symptoms during the study day and 24 (15%) patients had no symptoms during testing. Sixty nine (48%) symptomatic patients had a positive SI for at least one symptom (16 (11%) with acid reflux and 53 (37%) with NAR) and 75 (52%) had a negative SI. A total of 171 (57%) typical GORD symptoms were recorded, 19 (11%) had a positive SI for acid reflux, 52 (31%) for NAR, and 100 (58%) had a negative SI. One hundred and thirty one (43%) atypical symptoms were recorded, four (3%) had a positive SI for acid reflux, 25 (19%) had a positive SI for NAR, and 102 (78%) had a negative SI. Conclusion: Combined MII-pH identifies the relation of reflux of all types to persistent symptoms and the importance of NAR in patients taking PPIs.

Twenty-four hour ambulatory simultaneous impedance and pH monitoring: a multicenter report of normal values from 60 healthy volunteers.

OBJECTIVES:Impedance monitoring is a new diagnostic method for gastroesophageal reflux disease (GERD) where multiple impedance electrode pairs are placed on a standard pH catheter. It detects reflux of a liquid and/or gas bolus into the esophagus, as well as its distribution, composition, and clearing. The aim of this collaborative study is to define normal values for 24-h ambulatory simultaneous impedance and pH monitoring (24-h Imp-pH), and compare bolus parameters by impedance monitoring to changes in [H+] measured by pH monitoring.METHODS:Sixty normal volunteers without GER symptoms underwent 24-h Imp-pH with impedance measured at six sites (centered at 3, 5, 7, 9, 15, and 17 cm above lower esophageal sphincter) and pH 5 cm above the LES. Reflux detected by impedance was characterized by the pH probe as either acid, weakly acidic, nonacid, or superimposed acid reflux. Proximal reflux was defined as reflux that reached the impedance site 15 cm above the LES.RESULTS:Reflux frequency was common upright (median-27, 25th and 75th quartile-16, 42), but rare recumbent (median-1; 0, 4). A median of 34% (14%, 49%) of upright reflux reached the proximal esophagus. There was a similar number of mixed composition (liquid + gas; 49%) and liquid-only reflux (51%). Acid reflux was two-fold more common than weakly acidic reflux (p < 0.001). Superimposed acid reflux and nonacid reflux were rare. Acid neutralization to pH 4 took twice as long as volume clearance measured by impedance.CONCLUSIONS:Combining impedance and pH monitoring improves the detection and characterization of GER. This study characterizes the frequency, duration, and extent of reflux in health and provides normal values for 24-h Imp-pH for future comparison with GERD patients.

Baclofen decreases acid and non-acid post-prandial gastro-oesophageal reflux measured by combined multichannel intraluminal impedance and pH

Background : Omeprazole controls acid but not non‐acid reflux. The GABA B agonist baclofen decreases acid reflux through the inhibition of transient lower oesophageal sphincter relaxations (TLESRs) and should similarly decrease non‐acid reflux. Using combined multichannel intraluminal impedance and pH (MII/pH), we compared acid and non‐acid reflux after placebo and baclofen.

Combined multichannel intraluminal impedance–pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication

Combined multichannel intraluminal impedance‐pH (MII‐pH) monitoring detects gastro‐oesophageal reflux and identifies acid and non‐acid reflux events. It can be used in patients with persistent symptoms on proton‐pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII‐pH monitoring.

Combined Multichannel Intraluminal Impedance and Manometry Clarifies Esophageal Function Abnormalities: Study in 350 Patients

BACKGROUND:Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a technique that uses an FDA-approved device allowing simultaneous evaluation of bolus transit (MII) in relation to pressure changes (EM).METHODS:During a 9-month period, beginning from July 2002 through March 2003, we prospectively performed combined MII-EM on all patients referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. Manometric findings were reported based on criteria described by Spechler and Castell for liquid swallows. MII findings were reported as having normal bolus transit if ≥80% (8/10) of liquid and ≥70% (7/10) of viscous swallows had complete bolus transit.RESULTS:Three-hundred fifty studies were evaluated from patients with a variety of symptoms having the following manometric diagnoses: normal manometry (125), achalasia (24), scleroderma (4), ineffective esophageal motility (IEM) (71), distal esophageal spasm (DES) (33), nutcracker esophagus (30), hypertensive lower esophageal sphincter (LES) (25), hypotensive LES (5), and poorly relaxing LES (33). None of the patients with achalasia and scleroderma had normal bolus transit. Fifty-one percent of patients with IEM and 55% of patients with DES had normal bolus transit while almost all (more than 95%) patients with normal esophageal manometry, nutcracker esophagus, poorly relaxing LES, hypertensive LES, and hypotensive LES had normal bolus transit. Dysphagia occurred most often in patients with incomplete bolus transit on MII testing.CONCLUSION:Esophageal body pressures primarily determine bolus transit with isolated LES abnormalities appearing to have little effect on esophageal function. MII clarifies functional abnormalities in patients with abnormal manometric studies.

The Role of Nonacid Reflux in NERD: Lessons Learned From Impedance-pH Monitoring in 150 Patients off Therapy

INTRODUCTION:Nonerosive reflux disease (NERD) is the most common form of gastroesophageal reflux disease. While the role of acid reflux has been established, the relevance of nonacid reflux in generating symptoms in NERD is unknown.AIM: To evaluate the diagnostic utility of impedance-pH monitoring in NERD patients.METHODS: Patients with typical reflux symptoms (heartburn and/or regurgitation) and normal endoscopy (NERD) underwent a combined impedance-pH monitoring off proton pump inhibitor (PPI) therapy. Previously investigated 48 healthy volunteers served as controls. Distal esophageal acid exposure (% time pH < 4), number of acid and nonacid reflux episodes, 2-min window symptom index (SI; positive if ≥ 50%), and symptom association probability (SAP; positive if ≥ 95%) were calculated.RESULTS: Between June 2004 and June 2007, 150 NERD patients (82 women, mean age 48 yr, range 18–78 yr) reported symptoms during the impedance-pH monitoring. NERD patients had more reflux episodes (median [25th–75th percentile]) compared with healthy volunteers (total: 46 [26–65] vs 32 [18–43], P < 0.05; acid: 29 [14–43] vs 17 [8.5–31.0], P < 0.05; and nonacid: 20 [15–27] vs 18 [13.5–26.0], P= NS). Sixty-three (42%) patients had abnormal % time pH < 4. Among 87 patients with normal % time pH < 4., 22 (15%) had a positive SAP for acid, 19 (12%) for nonacid reflux, and 7 (5%) for both. Classifying patients with symptomatic nonacid reflux as having a hypersensitive esophagus reduced the number of patients with functional heartburn from 65 (43%) to 39 (26%).CONCLUSION: Monitoring for nonacid reflux in NERD patients reduces the proportion of patients classified as having “functional heartburn.” Studies assessing the clinical implications of these findings are warranted.

Functional Heartburn has more in common with Functional Dyspepsia than with Non-Erosive Reflux Disease

Introduction: Functional dyspepsia and non-erosive reflux disease (NERD) are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic symptoms in various subgroups of NERD are available. Aim: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring (MII-pH). Methods: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off proton pump inhibitor treatment. Oesophageal acid exposure time (AET), type of acid and non-acid reflux episodes, and symptom association probability (SAP) were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. Results: Of 200 patients with NERD (105 female; median age, 48 years), 81 (41%) had an abnormal oesophageal AET (NERD pH-POS), 65 (32%) had normal oesophageal AET and positive SAP for acid and/or non-acid reflux (hypersensitive oesophagus), and 54 (27%) had normal oesophageal AET and negative SAP (functional heartburn). Patients with functional heartburn had more frequent (p<0.01) postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. Conclusion: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the concept that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from patients with NERD in whom symptoms are associated with gastro-oesophageal reflux.

Gastroesophageal reflux and pulmonary fibrosis in scleroderma: a study using pH-impedance monitoring.

RATIONALE Interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) is associated with increased morbidity and mortality. Gastroesophageal reflux (GER) is considered a contributing factor in the pathogenesis of ILD. OBJECTIVES To characterize GER (acid and nonacid) in patients with SSc with and without ILD. METHODS Patients with SSc underwent pulmonary high-resolution computer tomography (HRCT) scan and 24-hour impedance-pH monitoring off-proton pump inhibitor therapy. The presence of pulmonary fibrosis was assessed using validated HRCT-scores. Reflux monitoring parameters included number of acid and nonacid reflux episodes, proximal migration of the refluxate, and distal esophageal acid exposure. Unless otherwise specified, data are presented as median (25th-75th percentile). MEASUREMENTS AND MAIN RESULTS Forty consecutive patients with SSc (35 female; mean age, 53 yr; range, 24-71; 15 patients with diffuse and 25 with limited SSc) were investigated; 18 (45%) patients with SSc had pulmonary fibrosis (HRCT score >or= 7). Patients with SSc with ILD had higher (P < 0.01) esophageal acid exposure (10.3 [7.5-15] vs. 5.2 [1.5-11]), higher (P < 0.01) number of acid (41 [31-58] vs. 19 [10-23]) and nonacid (25 [20-35] vs. 17 [11-19]) reflux episodes, and higher (P < 0.01) number of reflux episodes reaching the proximal esophagus (42.5 [31-54] vs. 15 [8-22]) compared with patients with SSc with normal HRCT scores. Pulmonary fibrosis scores (HRCT score) correlated well with the number of reflux episodes in the distal (r(2) = 0.637) and proximal (r(2) = 0.644) esophagus. CONCLUSIONS Patients with SSc with ILD have more severe reflux (i.e., more reflux episodes and more reflux reaching the proximal esophagus). Whether or not the development of ILD in patients with SSc can be prevented by reflux-reducing treatments needs to be investigated.

Esophageal function testing with combined multichannel intraluminal impedance and manometry: multicenter study in healthy volunteers.

BACKGROUND & AIMS Combined multichannel intraluminal impedance and manometry (MII-EM) assesses esophageal function by simultaneous measurement of both pressure and bolus transit. Normative data for this method have not been published. The aim of this study was to establish normative data for combined MII-EM and to correlate liquid and viscous bolus transit by impedance with esophageal contractions by manometry. METHODS Forty-three normal volunteers recruited from 4 centers (15 women, 28 men; age range, 21-72 years) underwent combined MII-EM with a catheter containing 4 impedance-measuring segments and 4 solid-state pressure transducers. Each center recruited and analyzed subjects independently, according to pre-established criteria. Each subject received 20 x 5 mL swallows, 10 liquid and 10 viscous material. Tracings were analyzed manually for bolus presence time, bolus head advance time, segmental transit times, total bolus transit time, contraction amplitude, duration, and onset velocity. RESULTS Ninety-seven and four-tenths percent of manometrically normal liquid and 96.1% of manometrically normal viscous swallows had complete bolus transit by impedance. Almost half (47.2%) of manometrically ineffective liquid and 34.7% of ineffective viscous swallows had complete bolus transit, whereas 91.7% of manometric simultaneous liquid swallows and 54.5% of simultaneous viscous swallows had complete bolus transit. More than 93% of normal individuals had at least 80% complete liquid or at least 70% complete viscous bolus transit. CONCLUSIONS This study establishes normative data for combined MII-EM. Combined MII-EM may be a more sensitive tool in assessing esophageal function compared to standard manometry because impedance can distinguish different bolus transit patterns. Studies in patients with manometrically defined esophageal motility abnormalities should help clarify the functional importance of manometric ineffective and simultaneous swallows.

Predictors of outcome in pancreatic duct disruption managed by endoscopic transpapillary stent placement

BACKGROUND The aim of this study was to identify predictors of outcome for pancreatic duct (PD) disruption managed by endoscopic transpapillary stent insertion. METHODS An endoscopy database was used to identify patients with PD disruption, defined as extravasation of contrast from the PD during ERCP. Data collected included demographic information, the results of imaging studies, management before endoscopic intervention, and outcomes after stent placement. Stents typically were exchanged at intervals of 6 to 8 weeks. Success was defined as clinical and pancreatographic resolution of the PD disruption. RESULTS Ninety-seven consecutive patients (34 women, 63 men; mean age, 53.7 [12.3] years) with PD disruption seen from 1995 to 2002 were identified. Causes of the disruption were the following: chronic pancreatitis (47), acute pancreatitis (44), operative injury (4), and trauma (2). Transpapillary PD stent insertion was technically successful in 92 (95%) patients; two underwent a combined cystenterostomy. The median duration of stent placement was 58 days (range 4-640 days). The outcome of stent insertion was successful in 52 patients (55%), unsuccessful in 32 (36%), and indeterminate in 8 (9%). On univariate analysis, a partially disrupted PD (p < 0.001), a disruption in the body of the pancreas (p = 0.04), a stent positioned to bridge the disruption (p < 0.001), and a longer duration of stent therapy (p = 0.03) were associated with a successful outcome. On multivariable logistic regression, only a partially disrupted duct and a stent bridging the disruption correlated with a successful outcome. Complications occurred in 6 patients. CONCLUSIONS Successful resolution of PD disruption by transpapillary stent insertion depends on the type of disruption and the ability to bridge the disrupted duct with a stent.