- Email: [email protected]
Increased Ex-VIVO Production of Pro-Inflammatory Cytokines by Esophageal Mucosa in Patients with Sensorimotor Esophageal Dysphagia
AGA Abstracts
intra-esophageal pressure >30 mmHg within at least 2 s) and esophageal shortening were analyzed during RDC. Symptoms were evaluated with Eckardt and GERD-Q scores. Causes of EGJOO were determined by reviewing patients' chart for previous history, complementary work up and treatment. Quantitative data were expressed as median (range) and qualitative data as percentage. They were compared using non parametric and Chi square tests. Results: 75 patients (2%) (31 males, mean age 59 years, range 24-88) were included. The dominant symptom was dysphagia (71%), regurgitation (13%), chest pain (5%), other (8%), no symptom (3%). Based on patients' work up and follow up, the causes of EGJOO were previous esophago-gastric surgery (49%, including fundoplication, bariatric surgery), incomplete form of achalasia (9%), neoplasia (7%), miscellaneous (17%; including hiatal hernia, Schatzki ring, eosinophilic esophagitis continuous positive airway pressure for sleep apnea) and unknown cause (17%). RDC was successfully performed in 68 patients and associated with pan-esophageal pressurization and esophageal shortening in 38% and 15% of them respectively. Eckardt score tended to be higher in patients with pressurization during RDC than in those without (6 (1-11) vs 4 (0-11), p=0.09) while there was no significant association with dominant symptom (p=0.66) or GERD-Q score (p=0.63). Median IRP and mean distal contractile integral (for 5-ml swallows) were similar in patients with or without pressurization while the percentage of 5-ml swallows associated with distal pressurization was higher in patients with pressurization after RDC (25 (0-100) vs 0 (0-100), p=0.01). No difference was observed for esophageal shortening. The percentage of patients with pressurization and shortening after RDC did not differ according to the cause of EGJOO (35% and 14% respectively of patients with previous surgery, 57% and 29% of achalasia, 18% and 9% of miscellaneous causes, 25% and 50% of neoplasia, 58% and 0% of unknown cause, p=0.59 and p=0.11). Conclusion: RDC test did not segregate patients with EGJOO in our series. Further prospective studies are necessary to determine the yield of RDC.
GEFV. Patients with both EGJ morphology type II or III and GEFV grade III or IV were classified as the high risk group. Patients with EGJ morphology type I and GEFV grade I or II were classified as the low risk group. The rest of patients were grouped in the intermediate risk group. Results: Among 67 patients assessed for TLESR, 38, 17 and 12 patients were classified as low, intermediate and high risk groups, respectively. A total of 50 patients (75%) had TLESR, and 102 TLESR events were observed. Only 5 TLESR events occurred in the supine position. The number of TLESR events in the intermediate and high risk groups was significantly higher than that in the low risk group (p<0.05, Figure 1). Out of 94 patients assessed for symptoms, 60, 22 and 12 patients were classified as low, intermediate and high risk groups, respectively. The prevalence of esophagitis was 8.3%, 31.8% and 75% in low, intermediate and high risk groups, respectively (p<0.05). Sensitivity and specificity of EGJ morphology and GEFV were 43% and 95% (EGJ morphology), and 76% and 75% (GEFV), respectively. The total scores of FSSG were 6.0, 4.0 and 4.5, respectively, in the three groups. Conclusions: EGJ morphology assessment has a low sensitivity but a high specificity. A combination assessment of EGJ morphology and GEFV is useful for assessing GERD and for predicting the frequency of TLESR. This assessment may be useful as a preoperative evaluation for GERD. EGJ morphology was not related to patients' symptoms.
Sa1675 LOW BASELINE IMPEDANCE IN PROXIMAL ESOPHAGUS AND DECREASED PSPW INDEX MAY RELATED WITH PATHOGENESIS OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS Joon Seong Lee, Tae Hee Lee, Su Jin Hong, Junseok Park, Seong Ran Jeon, Hyun Gun Kim, Jin-Oh Kim, Hyun-Sook Kim Backgrounds/Aims. Interstitial lung disease (ILD) is a common but fatal complication of systemic sclerosis (SSc). Gastroesophageal reflux disease (GERD) may be related to pathogenesis of ILD, but some study failed to show relationship between acidic GER and ILD. Our aims are to find relevant reflux parameters related to ILD in patients with SSc using highresolution esophageal manometry (HRM) and multichannel intraluminal impedance and pH monitoring (MII-pH). Methods. Of the consecutive 16 female patients with SSc, 9 patients showed ILD (SSc-ILD, median age 45 years, range 25-55) by HRCT and 7 patients didn't (SSc-N, age 49.5 y, 31-62). They all received esophageal HRM (Given Imaging, Los Angeles, CA, USA) and MII-pH (Sandhill Scientific, Inc.; Highland Ranch, CO, USA). We compared HRM parameters (Chicago ver 3.0) and MII-pH parameters including baseline impedance (BI) and post-reflux swallow-induced peristaltic wave (PSPW) index between two groups. Results. SSc-ILD showed significantly low FVC%pred and DLCO% compared with SSc-N (mean± SD, 72.2±17.1% vs. 101.3±14.2; 56.1±12 vs. 71.9±13.2, respectively, P<0.05) In HRM, absent contractility, ineffective esophageal motility and normal peristalsis were 6, 2, 1 in SSc-ILD and 1, 4, 2 in SSc-N. LES pressure was significantly low in SSc-ILD compared with SSc-N (13.7±6.4 vs. 24.0±11.3 mmHg, p<0.05). IRP, DCI, and UES pressure were not different between two groups. In MII-pH, all reflux % time using pH and impedance according to acidity or position, number of reflux events, and proximal extent were not different between two groups. However, mean bolus clearance time was longer in SSc-ILD than SSc-N [median 14 sec (IQR 13-28) vs. 11 sec (8.5-12.8), p<0.05]. BI except the most distal esophagus were significantly low in SSc-ILD than SSc-N (1099.2±327V vs. 2066.1±754.6V, 1032.9±483.2V vs. 2118.4±724.2V, 1190.7±745.3V vs. 2498.3±528.2V , p<0.005; 1257.8±959.7V vs. 2695.7±841.2V , P<0.01; 1239.9±907.4V vs. 2327.9±542.3V , P<0.05 at 17, 15, 9, 7, and 5 cm above the LES). PSPW index was significantly low in SSc-ILD than SSc-N [median 0 (IQR 0-0.03) vs. 0.16 (0.07-0.45), p<0.05]. Conclusion. Pathogenic mechanisms of ILD in SSc may relate to proximal esophageal reflux (low proximal esophageal BI) and decreased clearance mechanisms due to esophageal involvement of SSc.
Sa1673 INCREASED EX-VIVO PRODUCTION OF PRO-INFLAMMATORY CYTOKINES BY ESOPHAGEAL MUCOSA IN PATIENTS WITH SENSORIMOTOR ESOPHAGEAL DYSPHAGIA Francesco Covotta, Andrea Cossu, Danilo Badiali, Ivano Biviano, Adriana Marcheggiano, Carola Severi, Stefano Pontone, Annamaria Pronio, Enrico Corazziari Background: Sensori-motor esophageal dysphagia (SMED), also referred to as endoscopy non-obstructive dysphagia, does not have a well defined pathogenesis and is associated with different esophageal motor dysfunctions1. In previous ex-vivo animal studies, incubation of normal esophageal strips with the pro-inflammatory cytokines IL-1β or IL-6 significantly reduced, up to 50%, the neurogenic muscle contraction2. In addition, extracellular matrix secretion by human esophageal fibroblasts was increased in response to IL-43. Aim of this study was to evaluate the ex-vivo cytokine secretion by esophageal mucosa in SMED patients and the association, if any, with esophageal motor function assessed at manometry. Methods: Endoscopy was performed and mucosal biopsy specimens were obtained from the mid and distal esophagus of 14 consecutive SMED patients (9 females, mean age 45 years ± 16 years) and 10 normal control subjects (7 females, mean age 50 years ± 16 years). High resolution manometry (HRM) was performed in 10 of the 14 patients. Cytokines content in organ culture medium was assessed by multiplex chemi-luminescence immunoassay. Results: Final histological diagnosis of SMED patients was eosinophilic esophagitis (4), exfoliative esophagitis (5), lymphocytic esophagitis (2), gastroesophageal reflux disease (1) and negative report (2). At HRM, 8 patients had the following motility disorders: disorders of esophagogastric junction outflow, major disorders of peristalsis and minors disorders of peristalsis in 3, 1 and 4 patients, respectively. When compared to controls, both IL-6 and IL-1β mucosal production was significantly higher in the SMED patients (p= .02 for IL-6, and p=.005 for IL-1b). The Eosinophilic esophagitis patient subgroup showed significantly higher mucosal production of IL-6 and IL-4 when compared to controls (p= .01 and p= .02, respectively). Conclusions: Patients with non-obstructive dysphagia have increased mucosal production of proinflammatory cytokines that can affect the sensori-motor function and thus altering esophageal muscle contraction. Eosinophililic esophagitis patients show increased mucosal production of IL-4, a pro-fibrotic cytokine possibly contributing to dysphagia via esophageal stiffness induction. In conclusion, inflammation of the esophageal mucosa is associated with, and may have a role in the origin of, sensori-motor esophageal alterations and the symptom of dysphagia. 1. Carlson DA et al. Neurogastroenterol Motil. 2016 Sep 20. doi: 10.1111/ nmo.12941 2. Rieder F et al. Gastroenterology. 2007 Jan;132(1):154-65 3. Rieder F et al. Gastroenterology 2014 May;146(5):1266-77.e1-9.
Sa1676 THE EFFECT OF BODY POSTURE ON ESOPHAGEAL PRESSURE FLOW METRICS IN HEALTHY CONTROLS Shobna J. Bhatia, Abhishek Sadalage, Akash Shukla, Jan F. Tack, Taher Omari, Nathalie Rommel Background : Normal values for high resolution manometry with esophageal pressure topography (HRM-EPT) have been generated from data obtained in supine posture. Also, the Chicago classification has been validated using swallows done in supine position. As swallowing is more physiological in the upright position, earlier studies have also determined normal values for EPT in the upright posture, and showed that peristaltic pressures are higher and that segmental defects are shorter in supine position as compared to those in upright position. To date, the effect of body position on esophageal pressure flow metrics has not been studied. We therefore performed high resolution impedance manometry (HRIM) in supine and sitting positions to assess the potential impact on esophageal and trans-EGJ bolus flow during deglutition. Methods: Esophageal HRIM was performed using a 36 pressure and 12 impedance solid-state manometry- impedance catheter (Medtronic) in subjects in the sitting and supine posture. Per subject, fifteen liquid swallows were assessed (20 s apart) in each body position. Pressure and impedance data from 540 swallows were analyzed using Matlabbased pressure-flow analysis software (AIMplot, T Omari). Statistical analysis: Data are presented as median [IQR]. After normality test, metrics of both body positions were compared using Wilcoxon signed rank testing with post-hoc correction (a>0.05, *p<0.05, **p<0.01, ***p<0.0001). Results: Eighteen healthy subjects (age 35.8 [10.9] years; 14 M), who consented to the study, were recruited. Pressure-flow metrics of the whole esophagus showed that peak pressures and intrabolus pressures were significantly increased in supine
Sa1674 RAPID DRINK CHALLENGE (RDC) DURING ESOPHAGEAL HIGH RESOLUTION MANOMETRY (HRM): IS IT USEFUL IN PATIENTS WITH ESOPHAGO-GASTRIC JUNCTION OUTFLOW OBSTRUCTION (EGJOO)? Sabine Roman, Aurelien Garros, Francois Mion Objectives: EGJOO is a heterogeneous disorder. It may correspond to an incomplete form of achalasia, be associated with mechanical obstruction or be of unclear clinical relevance. Rapid drink challenge (RDC) is a simple test to perform during esophageal HRM. Our aim was to assess the yield of RDC in patients with EGJOO. Methods: From a database of 3066 consecutive HRM performed from 01/2012 to 09/2016, we extracted patients with EGJOO according to the Chicago Classification v3.0 (integrated relaxation pressure (IRP) > 15 mmHg without achalasia criteria). HRM protocol consisted of 10 5-ml water swallows in supine position and RDC test in sitting position. Esophageal pressurization (defined as homogeneous
AGA Abstracts
S-328
intra-esophageal pressure >30 mmHg within at least 2 s) and esophageal shortening were analyzed during RDC. Symptoms were evaluated with Eckardt and GERD-Q scores. Causes of EGJOO were determined by reviewing patients' chart for previous history, complementary work up and treatment. Quantitative data were expressed as median (range) and qualitative data as percentage. They were compared using non parametric and Chi square tests. Results: 75 patients (2%) (31 males, mean age 59 years, range 24-88) were included. The dominant symptom was dysphagia (71%), regurgitation (13%), chest pain (5%), other (8%), no symptom (3%). Based on patients' work up and follow up, the causes of EGJOO were previous esophago-gastric surgery (49%, including fundoplication, bariatric surgery), incomplete form of achalasia (9%), neoplasia (7%), miscellaneous (17%; including hiatal hernia, Schatzki ring, eosinophilic esophagitis continuous positive airway pressure for sleep apnea) and unknown cause (17%). RDC was successfully performed in 68 patients and associated with pan-esophageal pressurization and esophageal shortening in 38% and 15% of them respectively. Eckardt score tended to be higher in patients with pressurization during RDC than in those without (6 (1-11) vs 4 (0-11), p=0.09) while there was no significant association with dominant symptom (p=0.66) or GERD-Q score (p=0.63). Median IRP and mean distal contractile integral (for 5-ml swallows) were similar in patients with or without pressurization while the percentage of 5-ml swallows associated with distal pressurization was higher in patients with pressurization after RDC (25 (0-100) vs 0 (0-100), p=0.01). No difference was observed for esophageal shortening. The percentage of patients with pressurization and shortening after RDC did not differ according to the cause of EGJOO (35% and 14% respectively of patients with previous surgery, 57% and 29% of achalasia, 18% and 9% of miscellaneous causes, 25% and 50% of neoplasia, 58% and 0% of unknown cause, p=0.59 and p=0.11). Conclusion: RDC test did not segregate patients with EGJOO in our series. Further prospective studies are necessary to determine the yield of RDC.
GEFV. Patients with both EGJ morphology type II or III and GEFV grade III or IV were classified as the high risk group. Patients with EGJ morphology type I and GEFV grade I or II were classified as the low risk group. The rest of patients were grouped in the intermediate risk group. Results: Among 67 patients assessed for TLESR, 38, 17 and 12 patients were classified as low, intermediate and high risk groups, respectively. A total of 50 patients (75%) had TLESR, and 102 TLESR events were observed. Only 5 TLESR events occurred in the supine position. The number of TLESR events in the intermediate and high risk groups was significantly higher than that in the low risk group (p<0.05, Figure 1). Out of 94 patients assessed for symptoms, 60, 22 and 12 patients were classified as low, intermediate and high risk groups, respectively. The prevalence of esophagitis was 8.3%, 31.8% and 75% in low, intermediate and high risk groups, respectively (p<0.05). Sensitivity and specificity of EGJ morphology and GEFV were 43% and 95% (EGJ morphology), and 76% and 75% (GEFV), respectively. The total scores of FSSG were 6.0, 4.0 and 4.5, respectively, in the three groups. Conclusions: EGJ morphology assessment has a low sensitivity but a high specificity. A combination assessment of EGJ morphology and GEFV is useful for assessing GERD and for predicting the frequency of TLESR. This assessment may be useful as a preoperative evaluation for GERD. EGJ morphology was not related to patients' symptoms.
Sa1675 LOW BASELINE IMPEDANCE IN PROXIMAL ESOPHAGUS AND DECREASED PSPW INDEX MAY RELATED WITH PATHOGENESIS OF INTERSTITIAL LUNG DISEASE IN SYSTEMIC SCLEROSIS Joon Seong Lee, Tae Hee Lee, Su Jin Hong, Junseok Park, Seong Ran Jeon, Hyun Gun Kim, Jin-Oh Kim, Hyun-Sook Kim Backgrounds/Aims. Interstitial lung disease (ILD) is a common but fatal complication of systemic sclerosis (SSc). Gastroesophageal reflux disease (GERD) may be related to pathogenesis of ILD, but some study failed to show relationship between acidic GER and ILD. Our aims are to find relevant reflux parameters related to ILD in patients with SSc using highresolution esophageal manometry (HRM) and multichannel intraluminal impedance and pH monitoring (MII-pH). Methods. Of the consecutive 16 female patients with SSc, 9 patients showed ILD (SSc-ILD, median age 45 years, range 25-55) by HRCT and 7 patients didn't (SSc-N, age 49.5 y, 31-62). They all received esophageal HRM (Given Imaging, Los Angeles, CA, USA) and MII-pH (Sandhill Scientific, Inc.; Highland Ranch, CO, USA). We compared HRM parameters (Chicago ver 3.0) and MII-pH parameters including baseline impedance (BI) and post-reflux swallow-induced peristaltic wave (PSPW) index between two groups. Results. SSc-ILD showed significantly low FVC%pred and DLCO% compared with SSc-N (mean± SD, 72.2±17.1% vs. 101.3±14.2; 56.1±12 vs. 71.9±13.2, respectively, P<0.05) In HRM, absent contractility, ineffective esophageal motility and normal peristalsis were 6, 2, 1 in SSc-ILD and 1, 4, 2 in SSc-N. LES pressure was significantly low in SSc-ILD compared with SSc-N (13.7±6.4 vs. 24.0±11.3 mmHg, p<0.05). IRP, DCI, and UES pressure were not different between two groups. In MII-pH, all reflux % time using pH and impedance according to acidity or position, number of reflux events, and proximal extent were not different between two groups. However, mean bolus clearance time was longer in SSc-ILD than SSc-N [median 14 sec (IQR 13-28) vs. 11 sec (8.5-12.8), p<0.05]. BI except the most distal esophagus were significantly low in SSc-ILD than SSc-N (1099.2±327V vs. 2066.1±754.6V, 1032.9±483.2V vs. 2118.4±724.2V, 1190.7±745.3V vs. 2498.3±528.2V , p<0.005; 1257.8±959.7V vs. 2695.7±841.2V , P<0.01; 1239.9±907.4V vs. 2327.9±542.3V , P<0.05 at 17, 15, 9, 7, and 5 cm above the LES). PSPW index was significantly low in SSc-ILD than SSc-N [median 0 (IQR 0-0.03) vs. 0.16 (0.07-0.45), p<0.05]. Conclusion. Pathogenic mechanisms of ILD in SSc may relate to proximal esophageal reflux (low proximal esophageal BI) and decreased clearance mechanisms due to esophageal involvement of SSc.
Sa1673 INCREASED EX-VIVO PRODUCTION OF PRO-INFLAMMATORY CYTOKINES BY ESOPHAGEAL MUCOSA IN PATIENTS WITH SENSORIMOTOR ESOPHAGEAL DYSPHAGIA Francesco Covotta, Andrea Cossu, Danilo Badiali, Ivano Biviano, Adriana Marcheggiano, Carola Severi, Stefano Pontone, Annamaria Pronio, Enrico Corazziari Background: Sensori-motor esophageal dysphagia (SMED), also referred to as endoscopy non-obstructive dysphagia, does not have a well defined pathogenesis and is associated with different esophageal motor dysfunctions1. In previous ex-vivo animal studies, incubation of normal esophageal strips with the pro-inflammatory cytokines IL-1β or IL-6 significantly reduced, up to 50%, the neurogenic muscle contraction2. In addition, extracellular matrix secretion by human esophageal fibroblasts was increased in response to IL-43. Aim of this study was to evaluate the ex-vivo cytokine secretion by esophageal mucosa in SMED patients and the association, if any, with esophageal motor function assessed at manometry. Methods: Endoscopy was performed and mucosal biopsy specimens were obtained from the mid and distal esophagus of 14 consecutive SMED patients (9 females, mean age 45 years ± 16 years) and 10 normal control subjects (7 females, mean age 50 years ± 16 years). High resolution manometry (HRM) was performed in 10 of the 14 patients. Cytokines content in organ culture medium was assessed by multiplex chemi-luminescence immunoassay. Results: Final histological diagnosis of SMED patients was eosinophilic esophagitis (4), exfoliative esophagitis (5), lymphocytic esophagitis (2), gastroesophageal reflux disease (1) and negative report (2). At HRM, 8 patients had the following motility disorders: disorders of esophagogastric junction outflow, major disorders of peristalsis and minors disorders of peristalsis in 3, 1 and 4 patients, respectively. When compared to controls, both IL-6 and IL-1β mucosal production was significantly higher in the SMED patients (p= .02 for IL-6, and p=.005 for IL-1b). The Eosinophilic esophagitis patient subgroup showed significantly higher mucosal production of IL-6 and IL-4 when compared to controls (p= .01 and p= .02, respectively). Conclusions: Patients with non-obstructive dysphagia have increased mucosal production of proinflammatory cytokines that can affect the sensori-motor function and thus altering esophageal muscle contraction. Eosinophililic esophagitis patients show increased mucosal production of IL-4, a pro-fibrotic cytokine possibly contributing to dysphagia via esophageal stiffness induction. In conclusion, inflammation of the esophageal mucosa is associated with, and may have a role in the origin of, sensori-motor esophageal alterations and the symptom of dysphagia. 1. Carlson DA et al. Neurogastroenterol Motil. 2016 Sep 20. doi: 10.1111/ nmo.12941 2. Rieder F et al. Gastroenterology. 2007 Jan;132(1):154-65 3. Rieder F et al. Gastroenterology 2014 May;146(5):1266-77.e1-9.
Sa1676 THE EFFECT OF BODY POSTURE ON ESOPHAGEAL PRESSURE FLOW METRICS IN HEALTHY CONTROLS Shobna J. Bhatia, Abhishek Sadalage, Akash Shukla, Jan F. Tack, Taher Omari, Nathalie Rommel Background : Normal values for high resolution manometry with esophageal pressure topography (HRM-EPT) have been generated from data obtained in supine posture. Also, the Chicago classification has been validated using swallows done in supine position. As swallowing is more physiological in the upright position, earlier studies have also determined normal values for EPT in the upright posture, and showed that peristaltic pressures are higher and that segmental defects are shorter in supine position as compared to those in upright position. To date, the effect of body position on esophageal pressure flow metrics has not been studied. We therefore performed high resolution impedance manometry (HRIM) in supine and sitting positions to assess the potential impact on esophageal and trans-EGJ bolus flow during deglutition. Methods: Esophageal HRIM was performed using a 36 pressure and 12 impedance solid-state manometry- impedance catheter (Medtronic) in subjects in the sitting and supine posture. Per subject, fifteen liquid swallows were assessed (20 s apart) in each body position. Pressure and impedance data from 540 swallows were analyzed using Matlabbased pressure-flow analysis software (AIMplot, T Omari). Statistical analysis: Data are presented as median [IQR]. After normality test, metrics of both body positions were compared using Wilcoxon signed rank testing with post-hoc correction (a>0.05, *p<0.05, **p<0.01, ***p<0.0001). Results: Eighteen healthy subjects (age 35.8 [10.9] years; 14 M), who consented to the study, were recruited. Pressure-flow metrics of the whole esophagus showed that peak pressures and intrabolus pressures were significantly increased in supine
Sa1674 RAPID DRINK CHALLENGE (RDC) DURING ESOPHAGEAL HIGH RESOLUTION MANOMETRY (HRM): IS IT USEFUL IN PATIENTS WITH ESOPHAGO-GASTRIC JUNCTION OUTFLOW OBSTRUCTION (EGJOO)? Sabine Roman, Aurelien Garros, Francois Mion Objectives: EGJOO is a heterogeneous disorder. It may correspond to an incomplete form of achalasia, be associated with mechanical obstruction or be of unclear clinical relevance. Rapid drink challenge (RDC) is a simple test to perform during esophageal HRM. Our aim was to assess the yield of RDC in patients with EGJOO. Methods: From a database of 3066 consecutive HRM performed from 01/2012 to 09/2016, we extracted patients with EGJOO according to the Chicago Classification v3.0 (integrated relaxation pressure (IRP) > 15 mmHg without achalasia criteria). HRM protocol consisted of 10 5-ml water swallows in supine position and RDC test in sitting position. Esophageal pressurization (defined as homogeneous
AGA Abstracts
S-328