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Pre-Operative Esophageal Motility Disorders are not Associated with Increased Risk of Dysphagia After Fundoplication
Table 1: Analysis of factors associated with redo fundoplication
AGA Abstracts
undergoing fundoplication for complex hiatal hernia repair, demonstrate that younger patients and those with erosive esophagitis are more likely to experience persistent symptoms after fundoplication. Univariable analysis of factors associated with symptom resolution
Su1069 FACTORS ASSOCIATED WITH NEED FOR RE-DO FUNDOPLICATION FOR COMPLEX HIATAL HERNIA REPAIR Zubin Arora, Sampurna Shakya, Tanmayee Benjamin, Carol Rouphael, Thomas W. Rice, Rocio Lopez, Prashanthi N. Thota
Statistics presented as Mean ± SD, Median [P25, P75] or N (column %). p-values: a=ANOVA, b=Kruskal-Wallis test, c=Pearson's chi-square test, d=Fisher's Exact test. Table 2: Analysis of factors associated with redo fundoplication
Background: Fundoplication with or without Collis gastroplasty is frequently performed for the repair of complex hiatal hernia. However, symptoms or hernia can recur in some patients requiring re-do fundoplication. Factors associated with re-do fundoplication surgery remain unclear. The aim of this study was to assess the factors associated with re-do fundoplication surgery. Methods: A retrospective review of records of all patients who underwent fundoplication surgery for complex hiatal hernia repair by a single thoracic surgeon (TWR) at our institution between January 1, 2006 and December 31, 2013 was performed. Patients were divided into 2 groups based on whether the surgery was an initial fundoplication or redo fundoplication. Differences between the 2 groups were analyzed using SAS (version 9.4, The SAS Institute, Cary, NC) and a p < 0.05 was considered statistically significant. Results: A total of 344 patients with a mean age of 59.6±13.6 years were included in the analysis of which 247 (71.8%) were female. 282 (78%) patients underwent their initial fundoplication surgery while 62 (18%) patients underwent a redo fundoplication during the study period. Most of the patients who underwent redo fundoplication had their initial surgery performed at other institutions. Table 1 presents the univariable analysis of factors associated with redo fundoplication. Patients undergoing redo fundoplication were younger, had a history of asthma and smoking, and a longer duration of follow up. Redo fundoplication was performed via open approach in all patients and was combined with Collis gastroplasty in 91.9%of the patients. Patients undergoing redo surgery were more likely to have a partial fundoplication (8.1% vs. 2.8%, p=0.028) as compared to those undergoing initial fundoplication. No significant differences in preoperative high resolution esophageal manometry (per Chicago 3.0 classification) and pH testing were seen between the two groups (Table 2). Conclusion: In our selected cohort of patients undergoing fundoplication surgery mainly for complex hiatal hernia, younger age, history of asthma and smoking and longer follow up duration were associated with need for redo fundoplication. Redo fundoplication were more often partial fundoplication via open approach and with simultaneous Collis gastroplasty as compared to initial fundoplication.
Statistics presented as Mean ± SD or N (column %). p-values: a=ANOVA, b=Fisher's Exact test, c=Pearson's chi-square test.
Su1070 PRE-OPERATIVE ESOPHAGEAL MOTILITY DISORDERS ARE NOT ASSOCIATED WITH INCREASED RISK OF DYSPHAGIA AFTER FUNDOPLICATION Zubin Arora, Sampurna Shakya, Thomas W. Rice, Rocio Lopez, Prashanthi N. Thota Background: Fundoplication with or without Collis gastroplasty for short esophagus is the standard surgical treatment for complex hiatal hernias. However, development of postoperative dysphagia is one of the complications after fundoplication. The effect of preexisting esophageal dysmotility on development of post-fundoplication dysphagia has not been well studied. The aim of this study was to identify the predictors of post-operative dysphagia after fundoplication. Methods: Retrospective chart review of all patients who underwent a complex hiatal hernia repair by a thoracic surgeon (TWR) at our institution between January 1 st 2006 and December 31 st 2013 was performed. Patients who had pre- and post op high resolution esophageal manometry (HREM) were included. Information regarding demographics, medical history, symptoms, indication, type of surgery and HREM findings was extracted. Results: A total of 344 patients were included in the analysis. Mean age was 59.6±13.6 years and 247 (71.8%) were female. Majority of patients had
S-463
AGA Abstracts
AGA Abstracts
paraesophageal hernia (178/344) and or a short esophagus for which 279 (81.1%) patients also underwent a simultaneous Collis gastroplasty. Sixty five patients had prior history of failed fundoplication. Twenty six (7.6%) patients complained of post fundoplication dysphagia. Univariable analysis of factors associated with development of post-fundoplication dysphagia is presented in Table 1. Patients with post-fundoplication dysphagia were younger (mean age 54.8±12.6 vs. 60.2±13.3 years, p=0.047), were more likely to have regurgitation (80.8% vs. 58.2%, p=0.024), and had a longer duration of follow up (median 47.1 vs. 11.2 months, p<0.001). Patients with post-fundoplication dysphagia were more likely to have undergone re-do fundoplication (30.8% vs. 17%, p=0.079), however, this trend did not reach statistical significance. There were no significant differences between various prefundoplication HREM parameters such as basal lower esophageal sphincter (LES) pressure, LES integrated relaxation pressure and esophageal motility disorders (per Chicago 3.0 classification) between the two groups (table 2). Conclusion: Our data, from a selected cohort of patients undergoing complex hiatal hernia repair, demonstrate that pre-operative HREM abnormalities are not associated with increased risk of post fundoplication dysphagia. Table 1: Analysis of factors associated with post-op dysphagia
Su1071 EFFICACY OF A POTASSIUM-COMPETITIVE ACID BLOCKER FOR IMPROVING SYMPTOMS IN PATIENTS WITH REFLUX ESOPHAGITIS, NON-EROSIVE REFLUX DISEASE, AND FUNCTIONAL DYSPEPSIA Daisuke Asaoka, Akihito Nagahara, Mariko Hojo, Kenshi Matsumoto, Hiroya Ueyama, Kohei Matsumoto, Kentaro Izumi, Tsutomu Takeda, Hiroyuki Komori, Yoichi Akazawa, Yuji Shimada, Taro Osada, Sumio Watanabe (Background and Aim) There are few reports about the efficacy of improvement of GERD and FD symptom by potassium-competitive acid blocker (PCAB) that was newly developed in Japan. The aim of this study is to investigate the efficacy of a potassium-competitive acid blocker (PCAB) named vonoprazan (VPZ) for improving symptoms in patients with reflux esophagitis (RE), non-erosive reflux disease (NERD), and functional dyspepsia (FD). (Methods) We conducted a hospital-based, retrospective study of outpatients in our department from March 2015 to August 2016. The patients who had to have heartburn, acid regurgitation, gastric pain, and/or a heavy feeling in the stomach of at least moderate severity at baseline were treated with 20 mg VPZ once daily for 4 weeks. The patients completed the Global Overall Symptom (GOS) scale to determine their symptom severity at baseline and after the 4-week treatment period. We evaluated the proportions of RE, NERD, and FD patients achieving improvement of their symptoms, defined as a GOS scale score of 1 [‘no problem'] or 2 [‘minimal problem']. We also evaluated the changes of the "GERD score", which was defined as the total points for heartburn and acid regurgitation on the GOS scale in RE and NERD patients, and the "FD score", which was defined as the total points for gastric pain and a heavy feeling in the stomach on the GOS scale in before and after 4-weeks therapy of VPZ therapy. (Results) Eighty-eight eligible cases were included in the study, comprising 20 RE, 25 NERD, and 43 FD patients. The rates of symptomatic improvement in RE, NERD, and FD patients were 75.0%, 60.0%, and 48.8%, respectively. In the cases who were firstly administered VPZ, the rates of symptomatic improvement were 90.9%, 66.7%, and 58.8% in RE, NERD, and FD patients, respectively. In the cases who were resistant to 8 weeks of proton pump inhibitor (PPI) therapy, the rates of symptomatic improvement were 55.6%, 53.8%, and 42.3% in RE, NERD, and FD patients, respectively. The GERD score in RE and NERD patients and the FD score in FD patients were both decreased after 4 weeks of VPZ therapy (p < 0.01). (Conclusions) In GERD and FD patients, the possibility that PCAB could be used as a new therapeutic drug was suggested.
Su1072 PHARMACOKINETICS, PHARMACODYNAMICS AND TOLERABILITY OF DWP14012, A NOVEL ACID PUMP ANTAGONIST, IN HEALTHY SUBJECTS Jaeseong Oh, SeungHwan Lee, Seol Ju Moon, Seung-Chul Lee, Areum Lee, In-Jin Jang Background DWP14012 is a novel acid pump antagonist being developed for the treatment of acid-related diseases as a potential alternative to proton pump inhibitors. This study aimed to evaluate the pharmacokinetics (PKs), pharmacodynamics (PDs), food effect and tolerability of DWP14012 after a single oral dose in healthy subjects. Methods A randomized, double-blind, placebo- and active-controlled, single ascending dose study (10, 20, 40, 80, 160, 320 mg) with a food interaction study in 160 mg dose group was conducted. Each group consisted of 12 subjects who were assigned to DWP14012, esomeprazole (active comparator), placebo in a ratio of 8:2:2. PK of DWP14012 was evaluated up to 48 h postdose and PD was evaluated through 24-h gastric pH monitoring before and after dosing. Tolerability evaluation including laboratory tests was conducted throughout the study. Results A total of 73 subjects were enrolled and 72 subjects were completed the study. Plasma concentration of DWP14012 reached the peak concentration at about 1 ~ 4 h postdose and fell mono-exponentially with a mean half-life of approximately 9 h. The systemic exposure of DWP14012 increased supra-proportionally. The increased gastric acid suppression according to dose of DWP14012 and clear exposure-response relationship were observed; the percentage of time pH≥4 was 3.8 %, 13.8 %, 44.6 %, 80.5 %, 91.3 % and 93.1 % in DWP14012 10, 20, 40, 80, 160, 320 mg dose group, respectively, whereas, the value was 9.3 % and 39.6 % in placebo and esomeprazole 40 mg dose group; the mean pH was 1.8, 2.3, 3.6, 5.2, 5.8 and 5.7 in DWP14012 dose groups, respectively, whereas, the value was 2 and 3.4 in placebo and esomeprazole group. DWP14012 showed rapid and sustained suppression of gastric acid secretion during 24 hours after dosing. Food did not influence on PK and PD of DWP14012. There were no serious adverse events and no clinically significant changes in tolerability parameters. Conclusion DWP14012 was well tolerated at doses up to 320 mg in healthy subjects, and the PK and PD properties evaluated in the first time in human represented the rapid and long-lasting gastric acid suppression effect of DWP14012. These results suggested that DWP14012 may be effective for the treatment of acid-related diseases.
Table 2: Analysis of high resolution esophageal manometry findings associated with postop dysphagia
Su1073 OMEGA-CUFF: A NOVEL IMPLANT TO AUGMENT THE LOWER ESOPHAGEAL SPHINCTER (LES) Robert A. Ganz, John Mehawej, Amy J. Peterson, Mark A. Rydell, Claude Tihon BACKGROUND: We investigated a novel device to treat GERD. The Omega-Cuff (Ω-Cuff; CT Resources, Eden Prairie, MN) is an omega (Ω) shaped, nitinol device with an open side, 1.2 cm in height/1.5 cm in diameter, surgically placed around the gastroesophageal junction (GEJ), and designed to augment the LES analogous to a partial fundoplication. METHOD: The Ω-Cuff was implanted in 31 pigs. In Phase 1, 7 pigs were used to assess different stiffness devices. With stiffer devices food boluses slowed when entering the device zone. A less stiff device with no food hesitation was then used in Phase 2, a 1-year study in which 24 pigs were implanted with the device. A laparotomy was performed and the LES region was exposed. The Ω-Cuff was applied onto the GEJ, positioned under the anterior vagus nerve, and sutured to the esophageal wall. Outcomes included animal growth, safety and changes in GEJ yield pressure. Yield pressure was assessed using a 2 cm long, 2 cm diameter balloon catheter. A deflated balloon was inserted transorally to the stomach. The balloon was inflated with 2ml of barium and slowly pulled back through the LES region toward
AGA Abstracts
S-464
AGA Abstracts
undergoing fundoplication for complex hiatal hernia repair, demonstrate that younger patients and those with erosive esophagitis are more likely to experience persistent symptoms after fundoplication. Univariable analysis of factors associated with symptom resolution
Su1069 FACTORS ASSOCIATED WITH NEED FOR RE-DO FUNDOPLICATION FOR COMPLEX HIATAL HERNIA REPAIR Zubin Arora, Sampurna Shakya, Tanmayee Benjamin, Carol Rouphael, Thomas W. Rice, Rocio Lopez, Prashanthi N. Thota
Statistics presented as Mean ± SD, Median [P25, P75] or N (column %). p-values: a=ANOVA, b=Kruskal-Wallis test, c=Pearson's chi-square test, d=Fisher's Exact test. Table 2: Analysis of factors associated with redo fundoplication
Background: Fundoplication with or without Collis gastroplasty is frequently performed for the repair of complex hiatal hernia. However, symptoms or hernia can recur in some patients requiring re-do fundoplication. Factors associated with re-do fundoplication surgery remain unclear. The aim of this study was to assess the factors associated with re-do fundoplication surgery. Methods: A retrospective review of records of all patients who underwent fundoplication surgery for complex hiatal hernia repair by a single thoracic surgeon (TWR) at our institution between January 1, 2006 and December 31, 2013 was performed. Patients were divided into 2 groups based on whether the surgery was an initial fundoplication or redo fundoplication. Differences between the 2 groups were analyzed using SAS (version 9.4, The SAS Institute, Cary, NC) and a p < 0.05 was considered statistically significant. Results: A total of 344 patients with a mean age of 59.6±13.6 years were included in the analysis of which 247 (71.8%) were female. 282 (78%) patients underwent their initial fundoplication surgery while 62 (18%) patients underwent a redo fundoplication during the study period. Most of the patients who underwent redo fundoplication had their initial surgery performed at other institutions. Table 1 presents the univariable analysis of factors associated with redo fundoplication. Patients undergoing redo fundoplication were younger, had a history of asthma and smoking, and a longer duration of follow up. Redo fundoplication was performed via open approach in all patients and was combined with Collis gastroplasty in 91.9%of the patients. Patients undergoing redo surgery were more likely to have a partial fundoplication (8.1% vs. 2.8%, p=0.028) as compared to those undergoing initial fundoplication. No significant differences in preoperative high resolution esophageal manometry (per Chicago 3.0 classification) and pH testing were seen between the two groups (Table 2). Conclusion: In our selected cohort of patients undergoing fundoplication surgery mainly for complex hiatal hernia, younger age, history of asthma and smoking and longer follow up duration were associated with need for redo fundoplication. Redo fundoplication were more often partial fundoplication via open approach and with simultaneous Collis gastroplasty as compared to initial fundoplication.
Statistics presented as Mean ± SD or N (column %). p-values: a=ANOVA, b=Fisher's Exact test, c=Pearson's chi-square test.
Su1070 PRE-OPERATIVE ESOPHAGEAL MOTILITY DISORDERS ARE NOT ASSOCIATED WITH INCREASED RISK OF DYSPHAGIA AFTER FUNDOPLICATION Zubin Arora, Sampurna Shakya, Thomas W. Rice, Rocio Lopez, Prashanthi N. Thota Background: Fundoplication with or without Collis gastroplasty for short esophagus is the standard surgical treatment for complex hiatal hernias. However, development of postoperative dysphagia is one of the complications after fundoplication. The effect of preexisting esophageal dysmotility on development of post-fundoplication dysphagia has not been well studied. The aim of this study was to identify the predictors of post-operative dysphagia after fundoplication. Methods: Retrospective chart review of all patients who underwent a complex hiatal hernia repair by a thoracic surgeon (TWR) at our institution between January 1 st 2006 and December 31 st 2013 was performed. Patients who had pre- and post op high resolution esophageal manometry (HREM) were included. Information regarding demographics, medical history, symptoms, indication, type of surgery and HREM findings was extracted. Results: A total of 344 patients were included in the analysis. Mean age was 59.6±13.6 years and 247 (71.8%) were female. Majority of patients had
S-463
AGA Abstracts
AGA Abstracts
paraesophageal hernia (178/344) and or a short esophagus for which 279 (81.1%) patients also underwent a simultaneous Collis gastroplasty. Sixty five patients had prior history of failed fundoplication. Twenty six (7.6%) patients complained of post fundoplication dysphagia. Univariable analysis of factors associated with development of post-fundoplication dysphagia is presented in Table 1. Patients with post-fundoplication dysphagia were younger (mean age 54.8±12.6 vs. 60.2±13.3 years, p=0.047), were more likely to have regurgitation (80.8% vs. 58.2%, p=0.024), and had a longer duration of follow up (median 47.1 vs. 11.2 months, p<0.001). Patients with post-fundoplication dysphagia were more likely to have undergone re-do fundoplication (30.8% vs. 17%, p=0.079), however, this trend did not reach statistical significance. There were no significant differences between various prefundoplication HREM parameters such as basal lower esophageal sphincter (LES) pressure, LES integrated relaxation pressure and esophageal motility disorders (per Chicago 3.0 classification) between the two groups (table 2). Conclusion: Our data, from a selected cohort of patients undergoing complex hiatal hernia repair, demonstrate that pre-operative HREM abnormalities are not associated with increased risk of post fundoplication dysphagia. Table 1: Analysis of factors associated with post-op dysphagia
Su1071 EFFICACY OF A POTASSIUM-COMPETITIVE ACID BLOCKER FOR IMPROVING SYMPTOMS IN PATIENTS WITH REFLUX ESOPHAGITIS, NON-EROSIVE REFLUX DISEASE, AND FUNCTIONAL DYSPEPSIA Daisuke Asaoka, Akihito Nagahara, Mariko Hojo, Kenshi Matsumoto, Hiroya Ueyama, Kohei Matsumoto, Kentaro Izumi, Tsutomu Takeda, Hiroyuki Komori, Yoichi Akazawa, Yuji Shimada, Taro Osada, Sumio Watanabe (Background and Aim) There are few reports about the efficacy of improvement of GERD and FD symptom by potassium-competitive acid blocker (PCAB) that was newly developed in Japan. The aim of this study is to investigate the efficacy of a potassium-competitive acid blocker (PCAB) named vonoprazan (VPZ) for improving symptoms in patients with reflux esophagitis (RE), non-erosive reflux disease (NERD), and functional dyspepsia (FD). (Methods) We conducted a hospital-based, retrospective study of outpatients in our department from March 2015 to August 2016. The patients who had to have heartburn, acid regurgitation, gastric pain, and/or a heavy feeling in the stomach of at least moderate severity at baseline were treated with 20 mg VPZ once daily for 4 weeks. The patients completed the Global Overall Symptom (GOS) scale to determine their symptom severity at baseline and after the 4-week treatment period. We evaluated the proportions of RE, NERD, and FD patients achieving improvement of their symptoms, defined as a GOS scale score of 1 [‘no problem'] or 2 [‘minimal problem']. We also evaluated the changes of the "GERD score", which was defined as the total points for heartburn and acid regurgitation on the GOS scale in RE and NERD patients, and the "FD score", which was defined as the total points for gastric pain and a heavy feeling in the stomach on the GOS scale in before and after 4-weeks therapy of VPZ therapy. (Results) Eighty-eight eligible cases were included in the study, comprising 20 RE, 25 NERD, and 43 FD patients. The rates of symptomatic improvement in RE, NERD, and FD patients were 75.0%, 60.0%, and 48.8%, respectively. In the cases who were firstly administered VPZ, the rates of symptomatic improvement were 90.9%, 66.7%, and 58.8% in RE, NERD, and FD patients, respectively. In the cases who were resistant to 8 weeks of proton pump inhibitor (PPI) therapy, the rates of symptomatic improvement were 55.6%, 53.8%, and 42.3% in RE, NERD, and FD patients, respectively. The GERD score in RE and NERD patients and the FD score in FD patients were both decreased after 4 weeks of VPZ therapy (p < 0.01). (Conclusions) In GERD and FD patients, the possibility that PCAB could be used as a new therapeutic drug was suggested.
Su1072 PHARMACOKINETICS, PHARMACODYNAMICS AND TOLERABILITY OF DWP14012, A NOVEL ACID PUMP ANTAGONIST, IN HEALTHY SUBJECTS Jaeseong Oh, SeungHwan Lee, Seol Ju Moon, Seung-Chul Lee, Areum Lee, In-Jin Jang Background DWP14012 is a novel acid pump antagonist being developed for the treatment of acid-related diseases as a potential alternative to proton pump inhibitors. This study aimed to evaluate the pharmacokinetics (PKs), pharmacodynamics (PDs), food effect and tolerability of DWP14012 after a single oral dose in healthy subjects. Methods A randomized, double-blind, placebo- and active-controlled, single ascending dose study (10, 20, 40, 80, 160, 320 mg) with a food interaction study in 160 mg dose group was conducted. Each group consisted of 12 subjects who were assigned to DWP14012, esomeprazole (active comparator), placebo in a ratio of 8:2:2. PK of DWP14012 was evaluated up to 48 h postdose and PD was evaluated through 24-h gastric pH monitoring before and after dosing. Tolerability evaluation including laboratory tests was conducted throughout the study. Results A total of 73 subjects were enrolled and 72 subjects were completed the study. Plasma concentration of DWP14012 reached the peak concentration at about 1 ~ 4 h postdose and fell mono-exponentially with a mean half-life of approximately 9 h. The systemic exposure of DWP14012 increased supra-proportionally. The increased gastric acid suppression according to dose of DWP14012 and clear exposure-response relationship were observed; the percentage of time pH≥4 was 3.8 %, 13.8 %, 44.6 %, 80.5 %, 91.3 % and 93.1 % in DWP14012 10, 20, 40, 80, 160, 320 mg dose group, respectively, whereas, the value was 9.3 % and 39.6 % in placebo and esomeprazole 40 mg dose group; the mean pH was 1.8, 2.3, 3.6, 5.2, 5.8 and 5.7 in DWP14012 dose groups, respectively, whereas, the value was 2 and 3.4 in placebo and esomeprazole group. DWP14012 showed rapid and sustained suppression of gastric acid secretion during 24 hours after dosing. Food did not influence on PK and PD of DWP14012. There were no serious adverse events and no clinically significant changes in tolerability parameters. Conclusion DWP14012 was well tolerated at doses up to 320 mg in healthy subjects, and the PK and PD properties evaluated in the first time in human represented the rapid and long-lasting gastric acid suppression effect of DWP14012. These results suggested that DWP14012 may be effective for the treatment of acid-related diseases.
Table 2: Analysis of high resolution esophageal manometry findings associated with postop dysphagia
Su1073 OMEGA-CUFF: A NOVEL IMPLANT TO AUGMENT THE LOWER ESOPHAGEAL SPHINCTER (LES) Robert A. Ganz, John Mehawej, Amy J. Peterson, Mark A. Rydell, Claude Tihon BACKGROUND: We investigated a novel device to treat GERD. The Omega-Cuff (Ω-Cuff; CT Resources, Eden Prairie, MN) is an omega (Ω) shaped, nitinol device with an open side, 1.2 cm in height/1.5 cm in diameter, surgically placed around the gastroesophageal junction (GEJ), and designed to augment the LES analogous to a partial fundoplication. METHOD: The Ω-Cuff was implanted in 31 pigs. In Phase 1, 7 pigs were used to assess different stiffness devices. With stiffer devices food boluses slowed when entering the device zone. A less stiff device with no food hesitation was then used in Phase 2, a 1-year study in which 24 pigs were implanted with the device. A laparotomy was performed and the LES region was exposed. The Ω-Cuff was applied onto the GEJ, positioned under the anterior vagus nerve, and sutured to the esophageal wall. Outcomes included animal growth, safety and changes in GEJ yield pressure. Yield pressure was assessed using a 2 cm long, 2 cm diameter balloon catheter. A deflated balloon was inserted transorally to the stomach. The balloon was inflated with 2ml of barium and slowly pulled back through the LES region toward
AGA Abstracts
S-464