Angela Anggiansah

Inclusion of solid swallows and a test meal increase the diagnostic yield of high resolution manometry (HRM) in patients with dysphagia

Introduction Standard manometry studies diagnose oesophageal dysmotility in patients presenting with dysphagia on the basis of a small number of small volume water swallows. The association of symptoms with abnormal pressure events strongly support the clinical relevance of manometry findings; however, patients report symptoms infrequently with 5–10 ml water swallows. Solid swallows and normal eating behaviour have not entered clinical practice because of the difficulty interpreting the complex pressure events and a lack of control values. The aim of this study was to assess the prevalence of symptomatic oesophageal dysfunction following individual liquid and solid bolus swallows and a standardised test meal in patients presenting with dysphagia and asymptomatic volunteers Methods 30 consecutive patients referred for investigation of endoscopy negative dysphagia and 23 healthy volunteers underwent HRM (Manoscan 360°, SSI) with 10 × 5 ml water and 5 × 1 cc bread swallows in the upright seated position. A test meal (cheese and onion pie: 500 Kcal, 34 g fat) was provided if patients consented and for 10 healthy volunteers Results Water and bread swallows were successful in 29/30 patients (12 M:18 F, age 16–86) and all healthy volunteers (11 M:12 F, age 20–56). 10 patients and 10 volunteers completed the test meal. No healthy subject had clinically significant dysmotility or complained of symptoms. 2/29 (7%) patients experienced their typical symptoms with water, 13/29 (45%) with bread (p = 0.023), 8/10 (80%) with the meal and 16/29 (55%) when results of bread and meal were combined (p = 0.008 compared to water swallows). A change in HRM diagnosis was made in 8/29 (28%) patients on the basis of solid compared to water swallows, of whom 5 (17%) complained of typical symptoms. When a meal was provided, there was a change in HRM findings in 7/10 patients compared to 5 ml water, of whom 4 complained of typical symptoms. When results were combined 10/29 (35%) showed a change in diagnosis and 5 had typical symptoms. Pathology that would have been missed with water swallows alone included: hypertensive contractility (2), spasm (2), variant achalasia (1) and increased resistance to flow at the gastro-oesophageal junction (3). The clinical relevance of 5/8 (62.5%) of these was confirmed with typical symptoms coincident with abnormal pressure events. Two patients with asymptomatic hypotensive dysmotility with water showed normalisation with solid swallows Conclusion The diagnostic yield and ability to associate symptoms with oesophageal dysfunction is increased with inclusion of solid swallows and a test meal compared to water swallows alone in patients with endoscopy-negative dysphagia

PTU-166 Diagnosis of Gastro-Oesophageal Reflux Disease (Gord) by Histology of Mucosal Biopsies from Distal Oesophagus: Agreement with Prolonged PH Monitoring

Introduction Prolonged wireless pH-monitoring (Bravo) increases diagnostic yield compared to 24 hr pH-studies. Studies have shown a weak association between oesophageal acid exposure from 24 hr pH-studies and mucosal disease on distal oesophageal histology. This study assessed the association between Bravo, endoscopic findings and distal oesophageal histology. Methods From July 2009 to August 2010, 63 consecutive patients with typical reflux symptoms had endoscopy with biopsies taken from 3 & 9 o’clock position at and 2cm proximal to the Z-line prior to pH capsule fixation 6cm proximal to the Z-line for prolonged (up to 96 hr) Bravo. All biopsies were assessed by the 6-parameter Zentilin histology score (Zentilin et al Gastroenterol 2005). GORDdiagnosis was based on “Average” acid exposure (Total Reflux; TR > 5.3% time pH < 4) over the time period measured and/or symptom-association (symptom index; SI > 50%) Results Adequate biopsy samples were available from 57/63 patients (mean age 44 (range 17–78); 27M). 37/57(65%) patients had GORD based on either TR (n = 30) or SI(n = 32). 20/57(35%) were both TR & SI negative (Functional Heartburn; FH). 18 FH patients had no mucosal changes, 2 had grade A oesophagitis. There was no difference in individual histology parameters between GORD vs. FH (p > 0.05) apart from increased ‘intra-epithelial neutrophils’ (IEN) at the Z-line (9/37 vs. 1/20 positive; p = 0.031) and 2cm proximally (6/37 vs. 0/20 positive; p = 0.012). The combined Zentilin histology score was also higher in GORD at the Z-line (p = 0.079) and 2 cm proximally (p = 0.05). Using GORD diagnosis from 96 hr Bravo as reference, ROC analysis revealed that, although sensitivity remained poor, specificity of GORD diagnosis based on histology improved with IEN and total histology score. With increased IEN, sensitivity was 30% at the Z-line and 20% 2 cm above while specificity was 92.6% at the Z-line and 100% 2cm proximally. For the optimal Zentilin histology score of ≥7, sensitivity was 40.5% at the Z-line and 18.9% 2cm above while specificity was 95% at the Z-line and 100% 2 cm proximally. Histology corroborated GORD diagnosis (based on positive TR) in 11/30 and 20/30 patients at the Z-line and in 6/30 and 11/30 patients 2 cm proximally. Conclusion Histology lacks sensitivity as a stand-alone diagnostic test; however high IEN or total histology scores have high specificity for GORD diagnosis based on pH-study results. Thus, routine biopsy of the distal oesophagus may be sufficient to diagnose GORD and obviate the need for ambulatory pH-studies in this subgroup of patients. Disclosure of Interest None Declared.

PTU-197 Diagnosis of gastro-esophageal reflux disease (GERD) and prediction of treatment response to proton pump inhibitors (PPI) by prolonged wireless ph monitoring: a prospective assessment: Abstract PTU-197 Figure 1

Introduction Increasing duration of pH studies improves consistency of GERD diagnosis but clinical utility of the method is not established. Aim: (1) to identify measurements from prolonged pH studies that discriminate healthy volunteers (HVs) and GERD patients (2) to compare prediction of PPI response from prolonged and standard measurement. Methods HVs and patients with reflux symptoms entered a prospective trial. Quality of life (RAND-36) and symptom severity (Eraflux) was assessed on and off PPI and after 2 weeks ×2/day PPI. Endoscopy recorded mucosal disease. Wireless pH system (Bravo®, Given Imaging) measured acid reflux and symptoms up to 4 days. Receiver Operating Curve (ROC) assessed prediction of PPI response. For each prediction 80% of patients were randomly selected as training set, remaining 20% constituted test set. This was repeated 200 times producing average ROC with SEs. Area under Curve (AUC) quantified quality of prediction. Results Complete data were available from 25/33 HVs (18F, age 20–56) and 70/108 patients (31F, age 18–77), >320 days in total. Oesophagitis was present in 9 HVs (32%: Grade A) and 26 patients (33%: Grade A=19, B=2, C-D=5). Acid exposure time was elevated (AET >5.6%) in 3 (12%) HVs and 35 (50%) patients. Eraflux off-PPI was >25 (consistent with GERD) in 60/63 patients and fell by mean 7 (95% CI 5 to 10) on PPI, 46% reported positive response (>3 fall). Diagnosis: Endoscopy, AET and reflux-symptom association analysis (Symptom Index (SI)) did not discriminate health/disease; but reflux-associated symptoms/day (nRS/Day) covered different ranges for HV and patients. Logistic regression with bootstrap validation identified that ≥3 RS/day corresponded to ∼50% probability that participant was a patient. PPI response: Clinical parameters and AET did not predict outcome. SI (9.2 vs 30.2, p=0.0023) and nRS/Day (1 vs 2.6, p=0.012) were higher in responders. RAND-36 scores for poor physical role and pain were higher in non-responders (p∼0.1). SI ROC had an AUC of 0.73 (CI 0.51 to 0.92). SI >25 was the optimal cut-off for identifying PPI responders (Abstract PTU-197 figure 1). Prediction quality from 24 h studies was lower (AUC 0.69) and CIs for all parameters were wider with lower CI.Abstract PTU-197 Figure 1 ROC for SI as predictor of PPI response. Error bars show SE. ROC with cross-validation is black line, without cross-validation is grey line (∼10% greater AUC). Conclusion Diagnostic consistency for all parameters increases with study duration. A simple count of nRS/Day best discriminates HVs from patients on pH studies. SI >25 provides single best prediction of PPI response; but quality of predictions was modest in this population with low PPI response. Competing interests None declared.

Symptom Association in Ambulatory Gastro-Esophageal Reflux Monitoring: A Systematic Analysis

Introduction The diagnosis of gastro-oesophageal reflux disease (GORD) by ambulatory reflux monitoring is based on oesophageal acid exposure time (AET) or temporal association of reflux events with patient symptoms. Several key issues required for reflux-symptom association, such as the most appropriate pH threshold and time window, have not been defined and current statistical analysis has important limitations: Symptom Index (SI) is a measure of an effect size, not of confidence. Symptom Association Probability (SAP) is a measure of confidence but not of size and applies the Fisher exact test inappropriately (dividing time into fixed intervals does not produce independent counts). This study presents a systematic assessment of symptom association in ambulatory gastro-oesophageal reflux monitoring data. Methods Acid reflux (pH) and symptom data were acquired by wireless pH recording (Bravo, Given Imaging). 163 consecutive patients presenting with predominantly typical reflux symptoms (heartburn, regurgitation) studied 2006–2009 with duration >3.7 days were studied (636 days). Data were exported in XML format, and analyzed by custom written program. A systematic analysis was performed. Results (1) Symptom markers A finite-state algorithm was developed to equalise patient responses, removing redundant markers in one pass with reflux detection. (2) pH threshold: Setting pH thresholds for reflux detection is not physiological and a weighted S-shaped (‘dose response9) curve could be more appropriate. This was assessed varying the centre and steepness of the curve to maximise association with SI and SAP. A steep S-curve almost indistinguishable to a threshold was found: maximum correlation SI pH threshold 4.5, correlation 0.55; SAP pH threshold 4.4, correlation 0.34. (3) time window: The frequency of reflux associated symptom markers was above baseline only during minute 1. The association in minute 2 was no higher than chance. (4) Over time (day 1–4) SI was stable; however SAP increased progressively. Both parameters increased with the frequency of reflux events. CI for SI were computed by assuming a binomial distribution (Agresti-Coull method). Conclusion A novel approach to symptom association of ambulatory reflux monitoring data is presented. Confounding due to redundant symptom markers is removed by a finite-state algorithm. Acid threshold of pH 4.5 and a time window of 1 min provided optimal correlation with SI. Computing SI with CI provides a statistically valid, single parameter that describes both size of effect and likelihood of association between reflux events and symptoms.

Increasing Reflux Study Duration Progressively Improves Diagnostic Consistency: A Prospective Study With 96hr Wireless pH Recordings

Introduction Previous studies suggest that prolonged ambulatory reflux monitoring can improve measurement consistency; however, previous reports were not analysed appropriately or adequately powered to determine the impact on key clinical parameters. The aim of this study was to assess measurement consistency for acid exposure time (AET) and symptom association with reflux events used to establish the diagnosis of GORD. Methods Acid reflux (pH) and symptom data were acquired by prolonged, 4 day, wireless pH recording (Bravo, Given Imaging). 163 consecutive patients presenting with predominantly typical reflux symptoms (heartburn, regurgitation) studied 2006–2009 with a record duration of >3.7 days were studied (636 days). Data were exported in XML format, redundant symptom markers were removed in one pass with reflux detection. A cross-validation procedure assessed measurement variability (standard deviation (SD)) and diagnostic consistency of AET, symptom index (SI) and symptom association probability (SAP). The 4-day records were divided into 1-day sections and re-assembled as all possible subsets. Index parameters were computed for all subsets and labelled with a sequence identifier in the database. Bias due to self-referential comparisons was excluded (i.e., day 1 was not compared with day 123) and, also, no comparisons with 4-day results are given. Standard diagnostic thresholds were applied. In addition, the effect of varying threshold pH value used for reflux detection on diagnostic consistency was assessed. Results Measurement variability: There was no change in AET or SI over time; however, SAP increased progressively with study duration. Standard deviation (SD) was higher for 1-day than 3-day records for AET (+50% (confidence interval (CI): 10%…120%)) and SI (+100% (CI 120%…270%)) with no important difference across the observed range. Results for 2 days were intermediate. Similar findings were present for SAP (1 day vs 3 days at 95% SAP (+100% (CI 10%…700%); however, for this parameter measurement variability increased exponentially as SAP approached 100%. Diagnosis: Consistency for GORD diagnosis increased with study duration (table 1) for all parameters studied. Conclusion Increasing the duration of reflux studies progressively improves diagnostic consistency for GORD based on both AET and reflux-symptom association analysis independent of diagnostic threshold applied.

The effect of bolus consistency and position change on the coordination of peristaltic contractions in healthy volunteers

Introduction Previous studies have shown that oesophageal contractility increases with workload (eg, swallowing solids); however mechanistic studies suggest that effective oesophageal clearance depends more on effective coordination between the proximal and distal peristaltic contractions at the proximal transition zone (PTZ) than contractile pressure per se. This study assessed the effects of bolus consistency and position change on coordination of oesophageal contractions as assessed by the PTZ physiology in healthy, asymptomatic volunteers using high resolution manometry (HRM). Methods 23 healthy volunteers (11M:12F, age 20–56) underwent HRM (Manoscan 360°, SSI) with 10×5 ml water and 21 with 5×1 cc bread swallows in the upright seated and supine positions. Measurements of the PTZ mean pressure and break in peristalsis length defined by 30 mm Hg isocontour were recorded. In addition, the length of the proximal contraction (upper oesophageal sphincter to start of PTZ) and distal contraction (end of PTZ to lower oesophageal sphincter) defined by 30 mm Hg isocontour and normalised to oesophageal length (%) were calculated. Results PTZ mean pressure increased from liquid to solid in the upright (12.3 (8.3–17.8) vs 20.3 (12.9–29.5) mm Hg; p Conclusion Increased bolus consistency and position change from upright to supine position both increase the coordination of peristaltic contraction in healthy subjects. This effect is achieved by promoting contractility in the distal segment. This response to ‘physiologic challenge’ may increase specificity of manometric studies and provide a useful test of the oesophagus9 ability to adapt to increased workload (eg, after fundoplication).

Inclusion of Solid Swallows and a Test Meal Increase the Diagnostic Yield of High Resolution Manometry (HRM) in Patients With Reflux Symptoms

Introduction Manometry is applied in patients with suspected gastro-oesophageal reflux disease (GORD) to exclude motility disorders as a cause of symptoms. Routine studies use a small number of small volume water swallows, however dysmotility and symptoms are more likely to occur with normal eating behaviour. This approach has not entered clinical practice because of difficulty interpreting complex pressure events during ingestion of solids and a standardised meal as well as a lack of control values. This study aimed to assess the prevalence of symptomatic oesophageal dysfunction following individual liquid and solid bolus swallows and a standardised meal in patients with reflux symptoms and asymptomatic volunteers. Methods 45 consecutive patients with predominant reflux symptoms and 23 healthy volunteers underwent HRM (Manoscan 360°, SSI) with 10×5 ml water and 5×1 cc bread swallows in the upright seated position. A test meal (cheese and onion pie; 500 kcal, 34 g fat) was provided if patients consented. Ambulatory reflux studies were performed in patients. Results Water and bread swallows were completed in 44/45 patients (16 M:28 F, age 32–76) and all healthy volunteers (11 M:12 F, age 20–56). 18 patients and 10 volunteers completed the test meal. No healthy subject had clinically significant dysmotility or symptoms during the study. There were no symptoms with water swallows. 14/44 (32%) complained of symptoms with bread (p =0.0013), 7/18 during the meal and 16/44 (36%) when results of bread and meal were combined (p=0.0006). Bread swallows and a test meal resulted in a change of manometry diagnosis in 18/44 (41%) patients. In 13 patients dysmotility was present with solid but not water swallows: hypertensive contractility (3), oesophageal spasm (4), resistance at the gastro-oesophageal junction (4), variant achalasia (1) and severe peristaltic dysfunction (1). Conversely, normal peristalsis was seen in 5 asymptomatic patients with hypotensive motility on water swallows. Symptoms were associated with oesophageal dysfunction during the test meal in 7/16 (44%) patients: hypertensive contractility (1), oesophageal spasm (3), and resistance at the gastro-oesophageal junction (3). Ambulatory reflux studies were completed in 40/45 patients and 18/40 (45%) patients had an objective diagnosis of GORD. A new diagnoses based on symptomatic dysmotility was present in 1/18 (6%) patients with GORD, and 6/22 (27%) patients without GORD (p=0.016). Conclusion The inclusion of solid swallows and a test meal increased the diagnostic yield of HRM in patients referred for investigation of reflux symptoms compared to standard water swallows, in particular, in the patient group without GORD on reflux studies.

Pharyngeal and Oesophageal Dysmotility and Dysfunction in Patients With Chronic Cough: Assessment by High-Resolution Manometry

Introduction Laryngopharyngeal reflux (LPR) of gastric contents is a cause of chronic cough; however the pathophysiology of this disease remains unclear. Conventional manometry has insufficient spatial resolution for the functional assessment of the pharynx, upper oesophageal sphincter (UOS) and coordination between the proximal and distal oesophageal contractions that clear refluxate from the laryngopharynx and proximal oesophagus. This study applied high resolution manometry (HRM) in patients with chronic cough with and without association to reflux events. Methods Consecutive patients referred for investigation of chronic cough in 2009 were reviewed. Patients with hiatus hernia, severe co-morbidity and previous oeosphageal surgery were excluded. Of 66 patients referred, 34 (52%) (21 F:13 M) were eligible. HRM (ManoScan 360, Sierra) with detailed analysis (ManoView 2.0, Sierra) of 10 water swallows was performed followed by 24-h ambulatory pH-monitoring. Of this group 21 patients had negative reflux-cough symptom association probability (SAP; group A) and 13 had positive SAP (group B). Results from 23 healthy controls were available for comparison. A secondary analysis to assess the association of gastro-oeosphageal reflux (GOR) disease and motility was performed. Results Mean patient age was 55±15 (19–77). Mean acid exposure time was similar in group A and B (4.9±6.5 vs 3.7±4.0; p=0.34) and a similar proportion had pathologic reflux >4.2% acid exposure/24 h (7/21, 4/13; p=0.198). Moreover there was no significant interaction between the presence of GOR on pH-monitoring and any measurement of pharyngeal or oesophageal motility in this population. There was no significant differences for baseline UOS pressure; however residual UOS intrabolus pressure on 5 ml water swallows was higher in group A and B than controls (−0.34±0.69 and 1.09±0.64 mm Hg vs −4.4±5.8 mm Hg; p The percentage of primary peristaltic contractions was lower in group B with reflux associated cough than groups A and C (56% vs 79% and 87%; p=0.03 and p Conclusion Detailed analysis of swallowing and oesophageal motility by HRM revealed changes to UOS and oesophageal function that impair clearance from the pharynx and oesophagus in patients with cough compared to healthy controls. These changes were most marked in patients in whom cough was associated to reflux events. These findings suggest that not only GOR but also impaired clearance of luminal contents from the pharynx and proximal oesophagus contribute to chronic cough.

Normal Values for Esophageal Motility and Function During Multiple Swallows of Low vs. High Viscosity Liquid

Introduction High resolution manometry (HRM) with spatiotemporal presentation of pressure data provides a detailed representation of oesophageal anatomy, motility and function. In the pharynx, raised Intrabolus pressure (IBP) with a steep intrabolus pressure gradient on HRM identifies clinically significant resistance to flow in the region of the upper oesophageal sphincter. The same principle can be applied to identify pathology that obstructs bolus passage also in the oesophagus and lower oesophageal sphincter (LOS); however larger volumes are required due to the greater capacity of the distal oesophagus. The sensitivity of this test to detect pathology may be increased by ingestion of high viscosity fluids compared to water; however normal values for these tests have not been established. The aim of this study was to compare oesophageal function with 200 ml high viscosity versus low viscosity liquid swallows in the physiologic, upright seated, position. Methods 9 healthy subjects (Male:Female 5:4, age 20–44) underwent HRM using a 36 channel solid state assembly (Manoscan 360, Sierra Scientific Instruments). After standard 10×5 ml water swallows, 200 ml of water (viscosity 1 cPois) and 200 ml of a thick lactose-free fruit-smoothie (100 kcal, ∼100 cPois) were ingested in consecutive order. Volunteers were asked to drink the liquid through a straw without stopping. Spatiotemporal plots of 5 ml water and large volume multiple swallows were assessed. Results are presented as Median (IQR). χ2 test was used for qualitative analysis and Wilcoxon test was used to for non-parametric quantitative group comparisons. Results A similar number of swallows were required to drink the high and low viscosity liquid (19.9 vs 17.9; p=0.4); however the duration required to ingest the smoothie was greater (35 s (33–49 s) vs 25 s (22–30 s; p=0.018). Complete suppression of oesophageal contractility was achieved for all water and 7/9 fruit-smoothie swallows. IBP was somewhat higher for 5 ml water swallows (8.9 mm Hg (6.7–13.8 mm Hg)) compared to 200 ml water (3.6 mm Hg (2.5–4.6)) and 200 ml smoothie (3.0 mm Hg (0.0–4.4 mm Hg)), although this difference was non-significant (p=0.109 and 0.139 respectively). A powerful postcontraction was observed in most patients after drinking the smoothie and water (8 vs 5/9 patients; p=0.294) followed by an increase in LOS postcontraction pressure (12.7 vs 7.1 mm Hg; p=0.144) respectively. Conclusion This study compares the function of the healthy oesophagus to free drinking of low versus high viscosity fluids. Furthermore it provides reference values for future clinical studies to assess the clinical utility of including high viscosity fluids in HRM investigation of patients with oesophageal symptoms.

The Pattern of Esophageal Acid Exposure and Esophageal Pressure Morphology in Patients With Hiatus Hernia

Introduction Gastro-oesophageal reflux disease (GORD) generally presents as pathological Upright, Supine or Bi-positional reflux. Hiatus hernia (HH) and dysmotility are common in chronic GORD. However, in the presence of HH, it is unclear how age, severity of oesophageal acid exposure and dysmotility are related to the different postural types of GORD. Methods From March 2006 to July 2010, 1242 patients with GORD symptoms had high resolution manometry (HRM; Manoscan 360, Sierra) and 24-h catheter-based pH-monitoring (Slimline™, Medtronic) performed. 124 consecutive patients with both pathologic reflux and HH were collected. Patients were classified as Upright (n = 24), Supine (n = 38) or Bi-positional (n = 62) predominant reflux. Total (TR > 4.2%), upright (UR > 8.15%) and supine (SR > 3.45%) reflux parameters were used to classify GORD into position subtypes. HH was defined as Type II (lower oesophageal sphincter (LOS)-crural diaphragm (CD), 1–2 cm) and Type III (LOS-CD > 2 cm) in accordance with the Chicago Classification. Student9s t test, χ 2 tests and Mann–Whitney-U test were used for statistical analysis. Results Mean ±SD age was 54 ± 14 years (range 16–85 years; 64 males). Patients with Bi-positional reflux (57 years) were older than those with Supine (49 years) (p = 0.013) or Upright reflux (53 years) (p = 0.04). Furthermore the severity of oesophageal acid exposure (TR, UR and SR) was greater in the Bi-positional (18.1%, 17.6%, 19.7%) than Supine (8.6%, 4.8%, 14.8%) (p Conclusion In patients with manometry-proven HH who present with symptoms suggestive of GORD, Bi-positional and Supine reflux predominance are associated with more severe disease and are more likely to be associated with failed peristalsis. Furthermore Bi-positional reflux disease is more common with increasing age as is Type III HH.