Tu1150 A Novel Methodology of Measuring Esophageal Distension From Multi-Channel Intraluminal Impedance Recordings

Fidings categories (p<0.05). Compared with the cc 2.0, the use of cc 3.0 resulted in an upstaging in category in 7/107 cases (6.5%. 5 cases changed from normal to IEM. 2 cases changed from FF to AC) and down staging in 16/107 (15.0%. 14 cases changed from minor findings (7 WL, 3 WS, 3 RNL and 1 HP) to normal. 2 cases of EGJOO changed to normal). Conclusion: cc 3.0 increases the number of normal studies basically due to lesser minor findings. As the clinical relevance of these minor findings is questionable, it is suggested that the cc 3.0 improves the specificity compared to cc 2.0 classification

Table 1. Contingency table for diagnostic categories according to Chicago 2.0 and 3.0

Tu1147 Acotiamide Has the Potential to Become a Promising Treatment for Patients With Esophagogastric Junction Outflow Obstruction Kazumasa Muta, Eikichi Ihara, Keita Fukaura, Xiaopeng Bai, Yoshimasa Tanaka, Kazuhiko Nakamura, Toshiaki Ochiai, Osamu Tsuchida, Hirotada Akiho, Ryoichi Takayanagi Background and Aim: Acotiamide hydrochloride is a newly developed prokinetic drug, which is thought to stimulate gastrointestinal motility by inhibiting acetylcholinesterase (AChE), and is approved to treat functional dyspepsia in Japan. In DDW2014, we reported that acotiamide affected esophageal motility. The precise effects of acotiamide on esophageal motility disorder (EMD) and its underlying mechanisms remain to be elucidated. The objective of the present study was to determine the effects of acotiamide on patients with EMD. Methods: Twenty-five patients (13 female and 12 male, mean age 63.6 ± 3.3 years) with suspected EMD were enrolled. Both esophageal body contractility and tone of the lower esophageal sphincter (LES) were evaluated by high-resolution manometry (Manoscan Z) based on distal contractile integral (DCI), basal LES pressure (respiratory mean) and integrated relaxation pressure (IRP) before and after 2 weeks preprandial administration of 100-mg acotiamide three times daily. For basic research, circular smooth muscle strips of porcine LES were prepared and direct effects of acotiamide on LES tone were examined. Results: According to the Chicago classification criteria, 3 patients were diagnosed with achalasia, 6 with esophagogastric junction outflow obstruction (EGJOO), 2 with absent peristalsis, 3 with distal esophageal spasm, 7 with frequently failed peristalsis, 2 with weak peristalsis, and 2 with normal esophageal function. Analysis of all the cases showed that acotiamide significantly reduced the extent of IRP (13.5 ± 1.38 vs 11.43 ± 0.85 mmHg) while it did not affect the extent of DCI (2004.3 ± 443.1 vs 1691 ± 429.3 mmHg-s-cm), when DCI was not applicable for patients with achalasia and absent peristalsis. By subgroup analysis, acotiamide significantly reduced the extent of IRP (21.1 ± 2.3 vs 11.5 ± 1.44 mmHg) but also that of DCI (3329.7 ± 1054.2 vs 2251.7 ± 66.4 mmHg-s-cm) in patients with EGJOO, and motility pattern returned to normal in most cases, based on Chicago classification criteria. The known pharmacological action of actiamide acotiamide as an AChE inhibitor could not explain the inhibitory effects of esophageal contractility. We examined the effects of acotiamide on LES contractility in vitro. Acotiamide (10 mM) significantly inhibited KClinduced contraction in circular smooth muscle strips of porcine LES, whereas pretreatment with 1-mM tetrodotoxin had no effects on this response, indicating that acotiamide directly affected the smooth muscles. Conclusions: Acotiamide normalizes impaired swallow-induced LES relaxation in patients with EGJOO via unknown mechanisms. Acotiamide has the potential to become a promising treatment for EGJOO.

Figure 1. Diagnostic categories according to Chicago 2.0 and 3.0 Tu1149 Anxiety and Impedance During Contraction in the Proximal Esophagus Are Significantly Associated With Bolus Perception in Healthy Control Individuals. Results of a Multicenter Study Using High Resolution Esophageal Impedance Manometry Daniel Cisternas, Taher Omari, Charlotte Scheerens, Nathalie Rommel, Jordi Serra, Ingrid Marin, Antonio Ruiz de Leon, Julio Perez de la Serna, Concepcion Sevilla, Albis C. Hani, Ana Maria Leguizamo, Alberto Rodriguez, Miguel A. Valdovinos, Jose Remes-Troche, Arturo Meixueiro, Ramiro Coello Jaramillo, Luiz Abrahao Junior, Eponina Maria de Oliveira Lemme, Claudio R. Bilder, Andres Ditaranto Introduction: Traditional manometric variables, whether standard or high resolution esophageal manometry, have not shown any correlation with bolus perception. Nevertheless, the role of pressurization dynamics or anxiety/depression on bolus perception during manometry are poorly characterized Aim: To determine predictors of bolus perception in healthy volunteers during esophageal manometry, using automated impedance manometry analysis (AIM) Methods: Healthy volunteers were recruited from nine centers. Standard water supine swallows were analyzed using HREM and HRIM. Bolus perception was recorded using a 5 points Likert scale (0-4). Pressurization dynamics was evaluated using AIM. Depression and Anxiety were evaluated using Hospitalized Anxiety and Depression scale (HAD) Results: 115 volunteers (57 females (49.6%)) with a total of 996 swallows were analyzed. 320 of this swallows were analyzed using impedance and HREM. Mean age was 32 years (18-69 years). Only 35/996 (3.5%) of swallows were symptomatic (Score 1=24 volunteers. Score 2=10 volunteers). Neither sex, age nor Body Mass Index showed any correlation with perception. Center of origin did predict perception: two centers (Veracruz and Bogota) showed a significantly higher perception scores. Perception showed a significant association with anxiety (r=0.18. p<0.001) and depression (r=0.11. p>0.001). None of the traditional manometric variables (IRP 4s, DCI, peristaltic gaps measurement, CVF and DL) showed association with perception. Bolus transport using dichotomous traditional impedance criterion was not associated with perception. None of the variables related to pressurization dynamics (peak pressure, pressure at nadir impedance, intrabolus pressure slope) showed correlation with perception. Impedance at peak pressure (during contraction) showed a significant association with perception when considered at the whole esophagus (r=0.128. p=0.015) and proximal esophagus (r= 0.166). P=0.02). On logistic regression, only HAD anxiety (x2=48.06. p=0.008) and impedance at peak pressure in the proximal esophagus (x2=17.59. p=0.001) showed a significant association with perception, while HAD depression and center of origin did not (p ns) Conclusion: Perception of symptoms during esophageal swallow seems to be determined by central mechanisms, as anxiety, and peripheral mechanisms, as esophageal impedance at peak pressure. Traditional manometric variables do not correlate with perception. The positive correlation between impedance at peak pressure and perception suggests that partial bolus entrapment rather than mucosal damage could trigger symptoms during swallowing. Proximal esophagus seems to be a significant determinant of the bolus perception.

Tu1148 Chicago 3.0 Classification Shows a Higher Specifity Than Chicago 2.0: Results of a Multicenter Study in Healthy Volunteers Daniel Cisternas, Luiz Abrahao Junior, Eponina Maria de Oliveira Lemme, Claudio R. Bilder, Andres Ditaranto, Jose Remes-Troche, Arturo Meixueiro, Jordi Serra, Ingrid Marin, Antonio Ruiz de Leon, Julio Perez de la Serna, Concepcion Sevilla, Albis C. Hani, Ana Maria Leguizamo, Alberto Rodriguez, Miguel A. Valdovinos, Ramiro Coello Jaramillo Introduction: It has been reported that the Chicago Classification leads to a significant number of non-normal findings in healthy individuals. Recently, an update of this classification has been published Aim: To compare the performance of Chicago Criteria versions 2.0 (cc 2.0) versus 3.0 (cc 3.0) in healthy individuals submitted to a High Resolution Esophageal Manometry (HREM) Methods: Healthy volunteers were recruited from nine centers. Standard water supine swallows were analyzed using HREM. Diagnosis were classified as in cc3.0 in heretical categories: Obstruction (Achalasia and EGJ Outflow Obstruction (EGJOO)), Major findings (Distal Esophageal Spasm, Absent Peristalsis (AP) or Absent Contractility (AC) and Jackhammer Esophagus (JACK)) , Minor Findings (Frequent Failed Peristalsis (FF), Weak Peristalsis with Small Defect (WS), Weak Peristalsis with Large Defects (WL), Ineffective Esophageal Motility (IEM), Fragmented Peristalsis (FP) , Rapid Contraction with Normal Latency (RNL)and Hypertensive Peristalsis (HP)) and Normal Results: 107 volunteers (57 (53.3%) females. Mean age 32 (18-69)) were recruited, and 972 swallows were analyzed. Using cc 2.0 criteria, the findings were as follows: Normal 71 (66.4%), EGJOO 8 (7.5%), JACK 1 (0.9%), FF 5 (4.7%), WS 13 (12.2%), WL 5 (4.7%), HP 1 (0.9%) and RNL 3 (2.8%). Using the cc 3.0 criteria the findings were: Normal 82 (76.6%), EGJOO 6 (5.6%), AC 2 (1.9%), JACK 1 (0.9%), IEM 16 (15.0%). Using the aforementioned heretical categories, cc 2.0 and cc 3.0 showed a significant difference (Kappa 0.522. p<0.001) (Table 1. Figure 1), basically because Cc 3.0 significantly augmented the Normal and diminished the Minor

Tu1150 A Novel Methodology of Measuring Esophageal Distension From MultiChannel Intraluminal Impedance Recordings Ali Zifan, Melissa M. Ledgerwood, Ravinder K. Mittal Background: Efficient esophageal bolus transport requires contraction of the segment of the esophagus behind the bolus and relaxation in front it, the two essential elements of peristaltic reflex. Contraction can be recorded using high resolution manometry (HRM). However, recording the relaxation limb of the peristaltic reflex during clinical esophageal manometry is difficult. Luminal distension during peristalsis is a surrogate of relaxation. Calculating CSA from X-ray fluoroscopy or intraluminal ultrasound (US) imaging is not

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detect the gene variations in each sample using a high-throughput sequencer. The variants detected by the high-throughput sequencer were confirmed by a direct sequencing procedure. Results: Seven variants were extracted by the high-throughput sequencer, and were analyzed using direct sequencing. Because the present study aimed to identify variants strongly associated with esophageal achalasia, variants were considered to indicate susceptibility to esophageal achalasia only when the variants were detected in all samples by both highthroughput and direct sequencing. Only the rs4898 T/C polymorphism was detected in all samples by both high-throughput and direct sequencing. Therefore, rs4898 was identified to indicate susceptibility to esophageal achalasia. This polymorphism is included in an intron of the synapsin 1 (SYN-1) gene and exon 5 of the tissue inhibitor of metalloproteinase-1 (TIMP-1). The polymorphism was detected in 16 of 21 patients with esophageal achalasia, including seven homozygous cases and nine heterozygous cases (76.2%), while seven of the 20 HVs, including five homozygous and two heterozygous cases (35.0%), were detected. The polymorphism was more frequently detected in female patients with esophageal achalasia. The age of onset and the need for surgical treatment were not associated with the frequency of the polymorphism. Conclusion: A genetic polymorphism, rs4898, in patients with esophageal achalasia was identified using a high-throughput sequencer with an original panel of target genes. The region of rs4898 is included in an intron of SYN-I, which is associated with the function of synapses, and in exon 5 of TIMP-I. The rs4898 polymorphism is considered to be a new risk marker for esophageal achalasia, and may be associated with the pathogenesis of esophageal achalasia through the altered expression of SYN-1 and/or TIMP-1.

AGA Abstracts

adequate, as the former entails ionizing radiation, while the latter can only measure distension at one location, and image analysis is arduous. Aim: Investigating and validating the Multichannel Intraluminal Impedance (MII) technique to measure luminal CSA of the esophagus during peristalsis using a novel methodology. Experimental Setup: Prior to the HRM/MII study, two saline solutions of different concentration (0.1N and 0.5N) were heated to body temperature (37°C), and their conductivities measured. First, 5 separate B-mode US images were obtained for 5 healthy subjects with US transducer positioned at 7cm above the LES during swallows of 5cc, 10cc and 15cc of water. Second, concurrent HRM/MII and US imaging was carried out with US transducer located 7cm above the LES. Eight swallows of two concentrations of saline solution of the previous volumes was recorded. The impedance recordings were also obtained in-vitro (37°C) in seven glass tubes of different CSAs with varying saline concentrations. Method: The proposed method comprises of consecutive swallows of two saline solutions of known conductivity into the esophagus to obtain two separate impedance values, allowing the calculation of CSA by solving two algebraic Ohm's Law equations. This combined with a correction factor estimated in-vitro, allows the calculation of the parallel impedance, and the CSA at the electrode pair site during maximal distension. Finally, iterative level-wise dynamic time warping of the two swallows is employed to temporally align, and calculate distension during the entire swallow.Results: In-vitro study showed a hyperbolic relation between impedance and test tube CSAs. The relationship between the impedance and %NaCl concentration was linear over a wide range of NaCl concentrations (Fig1 (a)). In-vivo studies show the correlation coefficient of 0.9655 between the US and the proposed impedance method (Fig1(b)). Bland-Altman plot of Fig 1(c) shows The SD was 12% of the mean of the two measurements. Since the latter differences are within ±2SD, the two methods can be used interchangeably. Conclusion: Measuring esophageal distension directly from multi-site impedance measurements using the proposed method can be a power tool, alongside manometry in diagnosing motility disorders related to lack of esophageal distension during peristaltic transport.

in the number of hospital discharges, length of stay and associated hospital costs over the study period was determined by using the chi square test for trends. RESULTS: In 1997, there were 2,493 admissions with a principal discharge diagnosis of achalasia as compared to 5,130 in 2012 (Z statistic: 7.88, p<0.001, Figure 1). The mean length of stay for achalasia decreased by 20 % between 1997 and 2012 from 5.0 ± 0.2 days to 4.0 ± 0.2 days (p<0.01, Figure 2). However, during this period the mean hospital charges increased by 353.4 % from $12723 ± 921 in 1997 to $44967 ± 2533 in 2012 (p<0.001, Figure 3). The aggregate charges (i.e., "national bill") for achalasia increased by 725.9 % from $32,020,083 ± 3,424,012 in 1997 to $232,451,909 ± 16,790,851 in 2012 (p<0.001). The percentage of national bill for achalasia discharges (national bill for achalasia/total national bill) has markedly increased over the last 16 years (0.008 % in 1997 versus 0.039 % in 2012). CONCLUSIONS: The number of inpatient discharges for achalasia and associated costs have significantly increased over the last 16 years in the United States. Inpatient costs associated with achalasia contribute significantly to the total healthcare bill. Further research on cost-effective evaluation and management of achalasia is required.

Figure 1

Figure 1: (a) Relationship between conductance(i.e., 1/impedance) and saline concentration in different tubes, (b) Scatter diagram of CSA using US versus the proposed impedance method (correlation coefficient (r), and error sum of squares(SSE)), (c) Bland-Altman difference plot for the pairwise comparisons of CSA using US and estimated using proposed method (mean differences (solid line) and 2SD limits (dashed lines)), (d) Ultrasound image sequence of a sample 5cc swallow at 7cm above LES (Esophageal wall boundary in red, and the mucosa in yellow), and its estimated CSA using proposed methods (blue), and US (red) on the right.

Figure 2 Tu1152 Characterization of Primary Esophagogastric Junction Outflow Obstruction Froukje B. van Hoeij, André Smout, Albert J. Bredenoord Esophagogastric junction (EGJ) outflow obstruction is a newly defined entity, characterized by an elevated relaxation pressure (IRP4) of the lower esophageal sphincter (LES) in combination with intact or weak peristalsis, such that the criteria for achalasia are not met. Little is known about symptoms, pathophysiology and preferred treatment of this rare disorder. In this study we further characterize patients with EGJ outflow obstruction. Methods We included 46 patients diagnosed with EGJ outflow obstruction on high-resolution manometry (HRM) in our tertiary referral hospital between 2012 and November 2014. Patients were divided into primary or secondary outflow obstruction. Results We found a secondary outflow obstruction in 13 patients (age 56 years [42-72] M:F 7:6). Causes were intrathoracic stomach (2x), paraesophageal hernia, Schatzki ring, esophageal cancer, metastasis, vascular compression, mitochondrial myopathy, gastric band (2x), fundoplication and atresia operation. We excluded these patients from further analyses. Primary EGJ outflow obstruction was diagnosed in 33 patients (age 57 years [22-81] M:F 7:26). Nineteen (58%) patients presented with retrosternal pain, 11 (33%) with dysphagia, 3 (9%) with other symptoms (cough, globus, dyspepsia). The median [IQR] for various HRM parameters was; IRP4 18.8 mmHg [18-23], intrabolus pressure (IBP) 8.5 mmHg [5-12], basal LES pressure 26.6 mmHg [22-32], distal contractile integral 967 mmHg·s·cm [569-1722] and distal latency 5.9 s [5.26.9]. IBP was elevated in 48% of patients. Peristaltic breaks were seen in 88% of patients, with a median length of 2.4 cm. None of the patients had stasis of food, difficult LES passage or luminal dilation on upper endoscopy. Only 7/23 patients (30%) had stasis on a timed barium esophagogram, they were older than patients without stasis (69 vs 57 years; p= 0.02). No differences in symptoms or HRM parameters were found between patients with or without stasis on barium swallow. In 27 patients (82%) no treatment was required: 21 had symptoms judged unrelated to outflow obstruction, six had spontaneous symptom relief. The remaining 6 patients were treated with variable efficacy. Intrasphincteric botox injections resulted in a good but short-lived effect in 4 patients (12%). Pneumatic dilatation was unsuccessful in 2 patients (6%). Two patients were later diagnosed with achalasia on the basis

Figure 2: Bolus transport visualization during peristalsis in the supine position of a pairwise 5cc saline compound swallow. Pressure is overlaid on the mesh with different shades ranging from dark blue (low) to dark red (high) pressure values. Tu1151 Increasing Inpatient Burden and Costs Associated With Achalasia: An Analysis of National Trends in the United States From 1997 to 2012 Vaibhav Wadhwa, Prashanthi N. Thota, Madhusudhan R. Sanaka BACKGROUND/AIMS: Achalasia is an uncommon esophageal motility disorder characterized by dysphagia, regurgitation, chest pain and weight loss. There is limited data on the rate and costs associated with inpatient admissions for achalasia. The aim of this study was to evaluate the incidence and associated costs of hospital admissions related to achalasia. METHODS: We analyzed the National Inpatient Sample Database (NIS) for all patients in which achalasia (ICD-9 code: 530.0) was the principal discharge diagnosis from 1997-2012. The NIS is the largest all-payer inpatient database in the United States containing data from approximately 8 million hospital stays each year. The statistical significance of the difference

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