Endoscopic Fundoplication With MUSE System

Study Overview
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Brief Summary
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This is a spontaneous, prospective, monocentric, observational, cohort study, with the aim of evaluating the effect of ultrasound-guided endoscopic fundoplication using the Medigus Ultrasonic Surgical Endostapler (MUSESystem; MediGus, Ltd. Israel) in patients with esophageal or extra-esophageal gastro-oesophageal reflux disease (GERD)-related symptoms. The end of the study will be at the end of the 6-year follow-up of the last patient enrolled. The study proposes the following objectives: Primary objective: to evaluate the efficacy of endoscopic fundoplication with MUSE for the treatment of GERD, through clinical experience, in terms of: effect on GERD-Health Related Quality of Life (HRQL) and Reflux Symptom Index (RSI) questionnaire scores effect on the use and dosage of proton pump inhibitors (PPI) feasibility and safety of the endoluminal fundoplication procedure Secondary objective: to characterize the treated patient population (demographic and objective data) and to identify the successful predictors of the procedure. The study design includes the following phases: *Preliminary patient evaluation and verification of inclusion criteria through: Upper GI endoscopy Esophageal high-resolution manometry 24-hours esophageal pH-impedance OFF PPI PPI use GERD-HRQL and RSI questionnaires scores OFF PPI 6-month follow-up: Upper GI endoscopy Esophageal high-resolution manometry 24-hours esophageal pH-impedance OFF PPI PPI use GERD-HRQL and RSI questionnaires scores OFF PPI 12-months follow-up: Upper GI endoscopy 24-hours esophageal pH-impedance OFF PPI PPI use GERD-HRQL and RSI questionnaires scores OFF PPI Yearly clinical follow-up (up to 6 years): PPI use GERD-HRQL and RSI questionnaires scores OFF PPI

Official Title
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Clinical Application of MUSE System for Ultrasound-guided Endoscopic Fundoplication for Gastro-esophageal Reflux Disease Patients

Conditions
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Gastro-esophageal Reflux, Endoscopic Fundoplication

Intervention / Treatment
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* Device: Endoscopic fundoplication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic (> 6 months) GERD-related esophageal or extra-esophageal symptoms Endoscopic or pH-impedance evidence of GERD (esophagitis, Barrett's esophagus, NERD, hypersensitive esophagus) Indication to surgical fundoplication Patients available for a long-term follow-up Exclusion Criteria: Hiatal hernia ≥ 3 cm Major esophageal motility disorder Esophageal stenosis Malignant neoplasia (except minor superficial skin neoplasm) Portal hypertension, bleeding disorders so to controindicate surgery, esophageal varices, stenosis or diverticula Previous cardiac, thoracic or upper GI surgery BMI >40 Pregnancy or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Endoscopic fundoplication|Endoscopic fundoplication is a less invasive alternative to the traditional surgical fundoplication. The MUSE device is similar to an endoscope, so the whole procedure can be done by a single operator. The device is composed of a shaft with a distal rigid part which is placed in the esophagus 3 cm proximal to the esophago-gastric junction containing a cartridge holding five B-shaped titanium surgical Staples and a tip which is retroflexed and contains an ultrasonic transducer which defines the correct tissue thickness for stapling the fundus against the esophagus. The device must be extracted to be reloaded with 5 more staples at a time for creation of a 180° anterior fundoplication.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 6 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 12 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 24 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 3 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 4 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 5 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score | GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes. | change from baseline GERD-HRQL at 6 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 6 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 12 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 24 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 3 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 4 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 5 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score | RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes. | change from baseline RSI at 6 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 6 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 12 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 24 months | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 3 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 4 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 5 years | 
| To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption | Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy | change from baseline PPI consumption at 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify endoscopic factors predicting positive outcomes: changes in hiatal hernia size | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The size of a hiatal hernia is a parameter describing the continence characteristics of the sphincter neo-valve. | change from baseline hiatal hernia size at 6 months | 
| To identify endoscopic factors predicting positive outcomes: changes in hiatal hernia size | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The size of a hiatal hernia is a parameter describing the continence characteristics of the sphincter neo-valve. | change from baseline hiatal hernia size at 12 months | 
| To identify endoscopic factors predicting positive outcomes: changes in Hill's grade | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The Hill's grade is a parameter describing the continence characteristics of the sphincter neo-valve. The Hill's grade range from I to IV; the higher grades represents worse outcomes (worse valve's continence). | change from baseline Hill's grade at 6 months | 
| To identify endoscopic factors predicting positive outcomes: changes in Hill's grade | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The Hill's grade is a parameter describing the continence characteristics of the sphincter neo-valve. The Hill's grade range from I to IV; the higher grades represents worse outcomes (worse valve's continence). | change from baseline Hill's grade at 12 months | 
| To identify endoscopic factors predicting positive outcomes: changes in Jobe's lenght | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The Jobe's lenght is a parameter describing the continence characteristics of the sphincter neo-valve. | change from baseline Jobe's lenght at 6 months | 
| To identify endoscopic factors predicting positive outcomes: changes in Jobe's lenght | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The Jobe's lenght is a parameter describing the continence characteristics of the sphincter neo-valve. | change from baseline Jobe's lenght at 12 months | 
| To identify endoscopic factors predicting positive outcomes: changes in esophagitis' grade | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The presence of esophagitis and its grade, as defined by the Los Angeles classification, is a parameter of procedure's efficacy. The esophagitis grade range from A to D; the higher grades represents worse outcomes. | change from baseline esophagitis' grade at 6 months | 
| To identify endoscopic factors predicting positive outcomes: changes in esophagitis' grade | Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The presence of esophagitis and its grade, as defined by the Los Angeles classification, is a parameter of procedure's efficacy. The esophagitis grade range from A to D; the higher grades represents worse outcomes. | change from baseline esophagitis' grade at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in DeMeester score | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. DeMeester score is a composite score which examined six variables (number of reflux episodes, number of episodes longer than 5 minutes, longest reflux duration, total percentage of monitoring time with pH below 4, and the percentage of time with pH below 4 in an upright position and supine position). A score of >14.72 shows a pathological reflux. Higher values represent worse outcomes. | change from baseline DeMeester score at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in DeMeester score | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. DeMeester score is a composite score which examined six variables (number of reflux episodes, number of episodes longer than 5 minutes, longest reflux duration, total percentage of monitoring time with pH below 4, and the percentage of time with pH below 4 in an upright position and supine position). A score of >14.72 shows a pathological reflux. Higher values represent worse outcomes. | change from baseline DeMeester score at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in AET (Acid Exposure Time) | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline AET at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in AET (Acid Exposure Time) | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline AET at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in longest reflux episode (min) | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline longest reflux episode at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in longest reflux episode (min) | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline longest reflux episode at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of refluxes greater than 5 minutes | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of refluxes greater than 5 minutes at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of refluxes greater than 5 minutes | parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of refluxes greater than 5 minutes at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of total refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of total refluxes at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of total refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of total refluxes at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of acid refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of acid refluxes at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of acid refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of acid refluxes at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of weakly acid refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of weakly acid refluxes at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of weakly acid refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of weakly acid refluxes at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of not acid refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of not acid refluxes at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of not acid refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of not acid refluxes at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of proximal refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of proximal refluxes at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in number of proximal refluxes | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline number of proximal refluxes at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in MNBI (Mean Nocturnal Baseline Impedance) | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline MNBI at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in MNBI (Mean Nocturnal Baseline Impedance) | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline MNBI at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in PSPW (Post Swallow reflux-induced Peristaltic Waves) | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline PSPW at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in PSPW (Post Swallow reflux-induced Peristaltic Waves) | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline PSPW at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in BCT (Bolus Clearance Time) | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline BCT at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in BCT (Bolus Clearance Time) | parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. | change from baseline BCT at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) basal pressure | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline LES basal pressure at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) basal pressure | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline LES basal pressure at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) lenght | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline LES lenght at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) lenght | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline LES lenght at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) IRP (Integrated Relaxation Pressure) | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline LES IRP at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) IRP (Integrated Relaxation Pressure) | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline LES IRP at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in DCI (Distal Contractile Integral) | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline DCI at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in DCI (Distal Contractile Integral) | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline DCI at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of peristaltic waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of peristaltic waves at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of peristaltic waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of peristaltic waves at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of weak waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of weak waves at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of weak waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of weak waves at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of fragmented waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of fragmented waves at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of fragmented waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of fragmented waves at 12 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of failed waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of failed waves at 6 months | 
| To identify pathophysiological factors predicting positive outcomes: changes in rate of failed waves | parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention. | change from baseline rate of failed waves at 12 months |