Mark D. Noar, M.D., M.P.H Heartburn and Reflux Study Center Baltimore, Maryland, USA

Transcription

1 The Rapidly Evolving GERD Universe: Expanding the Understanding of the Pathogenesis, Spectrum of Disease and Therapeutic Options of the 21st Century and Beyond Mark D. Noar, M.D., M.P.H Heartburn and Reflux Study Center Baltimore, Maryland, USA Beginning of the GERD Spring What is GERD? Why do we Care? How does GERD occur? What is the Spectrum of Disease? y treat How do we currently GERD? How will we be treating GERD? 1

2 ...Endoscopic therapy back in the game. f i treatment off patients i future success in with GERD symptoms depends on appropriate sub-classification of this heterogeneous disease, with targeted strategies based on pathophysiology, natural history, and d response to treatment. PRATEEK SHARMA and PHILIP KATZ Gastroenterology Feb 2015 Transoral Fundoplication vs. Omeprazole ITT Sham Randomized Control Trial Outcome Variable TF/Placebo group (n=87) Pre P-value Post Sham/PPI group (n=42) Pre P-value TIF vs PPI P-value Post Subjective Measurements Regurgitation Scores P< P<.001 P =.072 Heartburn Scores P< P<.001 P =.936 Regurgitation + Heartburn Scores P< P<.001 P =.313 Objective Measurements % time ph< P< P=NS P =.003 DeMeester score P< P=NS P =.005 # reflux episodes P< P=NS P =.004 Hunter, Kahrilas, et al., Gastroenterology

3 GERD The What and When MONTREAL DEFINITION OF GERD GERD is a common condition that occurs when gastric refluxate into the esophagus g p g causes troublesome symptoms or complications Vail N et al, Am J Gastroenterology 2006 NATURAL DEVELOPMENTAL HISTORY OF REFLUX Incompletely developed anatomy at birth Reflux begins at birth Gut G t maturity t it for f some 5-6 million pediatric patients have refractory GERD Reflux never stops million symptomatic adults Esophageal and Extra Extra--esophageal 3

4 Reflux Natu Naturally a y occu occurringg human u a co condition dto Variable presentation Chronic Degenerative Disease A degenerative disease is a disease in which the function or structure of the affected tissues or organs will increasingly deteriorate over time, whether due to normal bodily wear or lifestyle choices such as exercise or eating habits. Reflux Chronic Degenerative Disease Disease Progression - Mechanism Repetitive over eating = gastric distention Effacement of inferior LES distended fundus w/les exposed to acid pocket Inflammatory damage to underlying sphincter Healing with cardiac metaplastic mucosa Permanent shorting of the LES Ratio of LES length to its pressure becomes inadequate to maintain competence Free unchallenged reflux occurs 4

5 Initial Sphincter Degenerative Changes GERD Why Do We Care? 5

6 Epidemiology of GERD The most common outpatient GI diagnosis (NAMCS, 2009) Incidence= %.45% Prevalence = %1 15.2% in Europe % in Eastern Asia % 20% of US population has GERD weekly3 7% of US population has GERD daily4-6 1Dent 2Jung. J Neurogastro Motil 2011; 17 et al, Gut 2005; 54 et al, Gastroenterol 1997; 112 4Nebel et al, Am J Dig Dis 1976; 21 5Sandler et al, Gastroenterol 2002; 122 6Rubenstein & Chen, Gastr Clin NA 2014; 43 3Locke Approch to Therapy Influences Outcome and Progression A PATIENTPATIENT-CENTERED APPROACH! The main objectives for therapy of GERD are: To restore the perceived quality of life To control symptoms To heal the lesions, when present To eliminate medication need To avoid complications Caliche & Scarpignato, Br Med J 1998 Interrupt Chronic Progression of Disease 6

7 RATIONALE FOR THERAPY OF GERD From a therapeutic perspective,, perspective GERD is a disorder of both motility and esophageal and/or laryngeal acid, alkaline or enzyme exposure. The signs signs,, symptoms, and clinical conditions result primarily from recurrent reflux of gastric contents into the esophagus or aeroaerodigestive pathways (acidic, pepsin and nonnon-acidic). Tytgat NJ et Al, APT 2007 GERD has an adverse impact on patients lives comparable to that of other chronic diseases Mean HRQL score (SF-36) Best 100 n=110 Asthma, n 110 Diabetes mellitus, n= Worst US population, n= Congestive heart failure, n= GERD endoscopynegative, n= GERD endoscopypositive, n 198 positive n=198 0 Physical Bodily Mental Vitality functioning pain health Role General Role Social physical health emotional functioning Wiklund et al. Expert Rev Pharmacoecon Outcome Res 2003;3:

8 Esophageal Adenocarcinoma What is GERD really? 8

9 GERD + ExtraExtra-Esophageal Reflux Overlapping continuum or mutually exclusive? Patients with hoarseness and chronic cough (airway symptoms) had Barrett s esophagus just as frequently (8%) as GERD patients with heartburn heartburn.. During gastroesophageal reflux, the contents of the upper digestive tract and stomach may reflux all the way up the esophagus, beyond the upper esophageal sphincter, and into the oropharynx Reavis,, et al. Ann Surg Reavis Surg,, 2004 Atypical GERD Extraesophageal Symptoms GERD may occur in as many as: 50% of patients with NonCardiac Chest Pain (NCCP) Noar, DDW, % of patients with chronic hoarseness patients with 82% adult p asthma and patients with chronic cough, dental erosions, exercise induced symptoms 9

10 Explaining the cause of GERD? Varied Presentations Evolving Pathophysiological Disease Concepts Esophageal Extra--Esophageal Extra Erosive Esophagitis Regurgitation Non--erosive Esophagitis Non Laryngitis or Chronic Cough Eosinophilic Esophagitis Hoarseness or Voice Disturbances p g Barrett s Esophagus Normal Mucosa Heartburn Bronchitis and/or Asthma-Asthma-Recurrent Pneumonia Normal Mucosa Dysphagia Sleep Apnea Normal Mucosa Chest Pain 10

11 Traditional Pathophysiology vs. Evolving Pathophysiological Disease Concepts - Acid which is refluxed into the esophagus causes id i off the th tight ti ht junctions j ti b t widening between squamous mucosal cells allowing entry of caustics leading to further damage. - Fails to explain full spectrum of disease - Acid Acid--Pepsin Interaction - Stability at ph >4 Location specific: Esophagus vs. vs Larynx - TRPV1 Receptor Mediated - May explain all presentations - LES Dual Sphincter Degradation - Multi Multi--factorial Pathogenesis Pepsin Subtypes - Isoenzymes Pepsin Isoenzyme % of Total Optimum ph Range 1 <5% <1% % A 6% 3B 70% 3C 4-5% 5 6-7% Active ph Level Stable to ph Stable to ph 7.3 Bardhan, et al, International J Otolaryngology, 5/

12 Transient Receptor Potential Vanilloid 1 (TRPV1) Neurally mediated mechanism of action Direct nerve stimulation = Heartburn I fl i d l b P and d Calcitonin C l i i Inflammation due to release off S Substance Gene Related Peptide ((CGRP) CGRP) Non Non--neurally mediated mechanism of action Release of platelet activating factor (PAF) (PAF) Inhibits release of acetylcholine Disrupts circular muscle contraction Directly cytotoxic - erosive or ulcerative esophagitis esophagitis.. Powerful chemo chemo--attractant of eosinophils - eosinophilic esophagitis. Cytokine induction of leukocyte mediators of inflammation IL--6, IL IL IL--1β, and H2O2, w/selfw/self-perpetuating circuit. Harnett et al J Neurogastroenterol Motil 12

13 Progression of Degenerative Changes McDonald, et al. Cell Mol Gastro Hepatol, 2015 Hill Grade of Hiatal Hernia Hill. Gastrointest Endosc 1996; 44:

14 LES Dual Sphincter Mechanism. GI Motility online (May 2006) doi: /gimo14 Neural pathways to the Dual LES Sphincter GI Motility online (May 2006) doi: /gimo14 14

15 Physiology of TLESR of the Dual LES Sphincter GI Motility online (May 2006) doi: /gimo14 GERD: Goals of Medical Therapy Working Hypothesis Normalization of intra intra--esophageal acid exposure leads to symptom resolution Improve symptoms - Up to 60% of Pts on a PPI remain symptomatic El Serag et al, Aliment Pharmacol Ther 2010; 32: 720- Heal H l esophagitis h ii Prevent relapse Prevent complications 15

16 Heartburn vs. Regurgitation Heartburn has been the dominant focus of symptom relief Heartburn responds well to PPIs Therapeutic gain ~ 41% 31 RCTs; n = 9,457 Regurgitation as primary endend-point 7 placebo controlled trials Therapeutic gain = 17% Kahrilas, Howden & Hughes, Am J Gastroenterol 2011; 106: Symptom Elimination Not Guaranteed by ph Normalization in GERD Symptom resolution does not equal normalization of esophageal ph Up to % of Pts have abnormal intra intra-esophageal acid exposure despite PPI Tx while asymptomatic Baldi et al, Dig Dis Sci 1989; 34: Katzka K k DA & Castell C ll DO. DO Am A J Gastroenterol G l 1994; : Ouatu--Lascar & Triadafilopolous Am J Gastro 1998; 93: 711 Ouatu Fass R, Sampliner RE, et al. Aliment Pharm Ther 2000; 14: Gerson LB, Boparai V, Ullah N, Triadafilopolous G. Aliment Pharmacol Ther 2004; 20: Lin & Triadafilopolous Dig Dis Sci 2014 Grigolon et al, J Clin Gastroenterol 2008; 42:

17 Symptoms and ph Normalization Correlate Inconsistently 50 Pts with GERD 39 male; 44 Caucasian; VA Pts Mean age = 58 yrs; 5 yrs of PPI use No Barrett s Asymptomatic on PPI Tx (5 different PPIs) 37 on BID PPI; 13 on QD PPI Dual sensor 2424-hr ph monitoring on PPI Tx Milkes, Gerson, Triadafilopolous, Am J Gastroenterol 2004; Symptoms and ph Normalization Correlate Inconsistently 25 Pts normalized esophageal acid exposure Mean DeMeester score = 4.3 Intraesophageal AET = 2% 25 Pts had persistent acid reflux Mean DeMeester score = Intraesophageal AET = 13% No differences noted for QD vs. BID PPI Milkes, Gerson, Triadafilopolous, Am J Gastroenterol 2004;

18 What does the future hold? Sphincter Targeted Therapy Interventional Sphincterology The practice of sphincter directed therapy Correct the degenerative effects of chronic reflux Restore natural sphincter function Restore barrier function Increase gastric yield pressure Control TLESRs Reverse premalignant conditions Prevent development of cancer Interventional Sphincterologist 18

19 Interventional Sphincterology Sphincter targeted treatments Internal LES Endoscopic sphincter regeneration Radiofrequency Stimulation Electrical stimulator Unknown External LES Endoscopic fundoplication Transoral incisionless fundoplication (TIF) Transoral anterior fundoplication Laparoscopic Nissen fundoplication Surgically implanted devices Magnetic sphincter augmentation Physical Restriction Radiofrequency Sphincter Regeneration 19

20 RF DELIVERY CATHETER Flexible Soft bougie tip (20 Fr) 6 mm shaft (20 Fr) 65 cm operating length Balloon/basket (max 3 cm) 5.5 mm Niti electrode needles Continuous irrigation and suction channel RADIOFREQUENCY GENERATOR Four independent channels Temperature and impedance monitoring p g Integrated irrigation Automated RF delivery Auto shut-off Graphical User Interface Real time data updated pdated each second Visual guide reminds user what area has been treated and where to treat next 20

21 RADIOFREQUENCY ENERGY DELIVERY Four levels antegrade: 1 cm above z-line 0.5 cm below z-line Two additional pull-back treatments in gastric cardia On average 14 sets of lesions are created in the region from 1 cm above the Z line to 2 cm below the Z line RADIOFREQUENCY ENERGY DELIVERY Controlled delivery of radiofrequency Target temperature at 80 is maintained Thermocouple monitoring and power output regulated by the MDRF1 Generator Auto shut-off for safety 21

22 Fundo Pre-fundoplication Post-fundoplication RF Therapy Mechanism of Action Restoration of Barrier Function 22

23 Low power RF energy delivered to tissue Multi-level treatment remodels LES and Gastric Cardia Function improved, reduced compliance, fewer TLESRs RF therapy remodels the musculature of the lower esophageal sphincter (LES) and gastric cardia cardia. RF treatment results in significant reductions in tissue compliance RF Therapy results in significant reduction in transient LES relaxations. Restores the natural barrier function of the LES Significantly reduces spontaneous regurgitation caused by TLESRs Edward D. Auyang, Patrice Carter, Thomas Rauth, Robert D. Fanelli, SAGES Guidelines Committee, Endoluminal Treatments for GERD, May 2013 How RF Affects Smooth Muscle The mechanism of RF delivery to smooth muscle at the cellular level in an animal model include: Structural changes to and growth of the smooth muscle (size and amount) and redistribution of the interstitial cells of Cajal. A change to stimulate myofibroblasts which directly influences the production of muscle. A change in the muscle fiber to connective tissue ratio, this ratio becomes higher because the amount of connective tissue decreases while muscle fiber tissue increases. Increase in Collagen 1 and decrease in Collagen 3 BEFORE TREATMENT AFTER TREATMENT Herman et al - Diseases of Colon and Rectum, Dec

24 Increased Thickness CANINES HUMANS Before Treatment Baseline controluntreated 5.2 mm ± months post-treatment 7.8 mm ± % mean increase in thickness of the GE junction (p<0.0001) After Treatment Kim M, GI Endoscopy 2003 De Angelis C, Repici A, Dughera L. UEGW Months Decrease in Compliance Excludes Fibrosis 24

25 Radiofrequency Energy Delivery to the GE Junction Corrects GERD Associated Gastroparesis Gastric Emptying % % Emptied at 90 minutes % months 90 min % emptied Baseline 90 min % emptied Noar, M.D., Surgical Endoscopy 2007 Radiofrequency Energy Delivery to the GE Junction Corrects GERD Associated Gastroparesis Gastroparesis Improvement 100% 0001 * p= % ** p = % 70% % patients 60% 50% * ** <50% emptying (90 min) <50% emptying (120 min) 40% Pre-Treatment Post-Treatment 30% 20% 10% 0% N =28 N=8 N = 10 N=1 Noar, M.D., Surgical Endoscopy

26 Dyspepsia Score Post-Treatment 5 *p< * * * Baseline (n=26) 6 months (n=26) 12 months (n=26) 24 months (n=18) Noar, M.D. The Heartburn and Reflux Center EGG Diagnosis Before and After Radiofrequency Therapy (RF) of the Lower Esophageal Sphincter and Cardia Region 60% * 51% 50% 47% * p < % 31% % 30% patients Pre-RFA 27% Post-RFA 20% 11% 10% 0% 15% 14% 4% n=12 n=23 Normal EGG n=21 n=14 Tachy-gastria n=5 n=2 Brady-gastria n=7 n=6 Mixed Dysrhythmia Noar, M.D., Surgical Endoscopy

27 Pre & Post RF Barrier Restoration RF Regeneration Clinical Data 27

28 Mechanism Data Sample A comparison of patients before vs. after treatment indicated that acid exposure decreased significantly (median decrease, 2.4%; P =0.01) between baseline and 12 months for all treated patients (both initial active treatment and crossed-over patients). - Corley et al At 12 months, the mean HRQL scores of those off medications, the LES basal pressure, the 24-hr ph scores, and the proton pump inhibitor (PPI) daily dose consumption were significantly improved from baseline... - Aziz et al Reduction in esophageal acid exposure Perry et al Surg Lap, Endo & Perc Tech Aziz et al 2010 Curr Opin Gastroenterol - RCT Arts et al 2007 Digestive Disease Science Mattar et al Surg Endosc Lufti et al Surg Endosc Cipoletta et al Surg Endosc Torquati et al Surg Endosc al 2004 Surg Endosc Triadafilopoulos et al. Houston et al Surg Endosc Richards et al Annals of Surgery Triadafilopoulos et al Gastrointest Endosc Corley et al Gastroenterology - RCT Reduction in transient LES relaxations Arts et al Am Journal of Gastroenterol - RCT Tam et al Gut Kim et al Gastrointestinal Endosc Decreased tissue compliance without fibrosis Arts et al Am Journal of Gastroenterol RCT Increase I iin LES wall ll thickness thi k DiBaise et al Am Journal of Gastroenterol Chang et al Gastrointestinal Endosc Kim et al Gastrointestinal Endosc Increased LES pressure Aziz et al Curr Opin Gastroenterol Meier et al Scandinavian Journal of Gastro Tam et al Gut Utley et al Gastrointest Endosc Durability Multiple 44-Year Follow Follow--Up Sustained improvement in symptoms of GERD & antisecretory drug use: 4-year followfollow-up of the RF energy procedure. 96 PATIENTS - 48 MONTHS 75% OFF ALL MEDICATION NO SERIOUS COMPLICATIONS Noar MD, Lotfi-Emran S. Gastrointest Endosc Mar; 65(3): Long-term results of RF energy delivery for treatment of GERD: sustained improvements in symptoms, quality of life, & drug use at 4-year follow-up. 83 PATIENTS - 48 MONTHS 86% OFF DAILY MEDICATIONS NO SERIOUS COMPLICATIONS Reymunde A, Santiago N. Gastrointest Endosc Mar;65(3):361-6 Long-term results of RF energy delivery for treatment of GERD. Results of a 48 month prospective study. 56 PATIENTS - 48 MONTHS 72% OFF ALL MEDICATION 1 TRANSIENT COMPLICATION Dughera et al, Diagnostic and Therapeutic Endoscopy, August

29 RF Stimulation 88-Year Durability Study Primary and Secondary Endpoints Primary Endpoints met > 50% improvement in the following: H tb i t Linkert Li k t scale) l ) Heartburn score (6 point Mean decrease of -1.8 points (P=0.003) GERD-HRQL (6 point Linkert scale) Mean decrease of -11 points (P=0.003) General QoL (SF-36) Mental mean increase 13 points (P=0.001) Physical meant increase 9 points (P=0.001) Secondary Endpoints 76.9% (P=0.0001) 76 9% off ff PPI s PPI entirely ti l (P ) Esophageal acid exposure, while improved at 4-year, returned to baseline at 8-year LES pressure not significantly impacted at 4 or 8 year All patients declared symptom control superior to drug therapy No disease progression, no evidence of Barrett s esophagus or CA Dughera et al. Gastroenterology Research and Practice Volume 2014 Article ID RF Stimulation 1010-Year Durability Study 217 patients Complete cohort g group p p ((CC)) 149 patients at 10 year cut-off 99 patients available for follow up Participant pool (PP) 72% w/extra-esophageal reflux 18 LNF failures 100% refractory to BID PPI BMI equally represented Long-term maintenance effect of radiofrequency energy delivery for refractory GERD: a decade later. M. Noar, P. Squires, E. Noar, M. Lee. Surgical Endoscopy e-published February 2014, print August

30 RF Regeneration 1010-Year Durability Study Primary and Secondary Endpoints Primary Endpoint Normalization of GERD-HRQL in 70% or greater of patients at 10 years. 72% (P < % confidence interval) Secondary Endpoints 50% reduction of PPI use (bid at baseline) at 10 years 64% with 41% off all meds/ppi s entirely (P < % confidence fid iinterval) t l) 60% increase in patient satisfaction at 10 years 54% (P < % confidence interval) No esophageal CA 85% reversal of existing Barrett s 10-Year 10Medication Use P <

31 10-Year 10GERD--Health GERD Related Quality--Of Quality Of--Life P < 10-6 P < Year 10Satisfaction 31

32 LPR vs. GERD 10 p=0.54 A LPR Non-LPR Satisfa action Score Medica ation Score p=0.052 B LPR Non-LPR edic ati Off Follow-Up (Years) on 30 p=0.17 C 25 LPR Non-LPR Me On 0.5 Me dic dic atio ati on n Follow-Up (Years) 3.5 Waking From Sleep Score On M GERD-HRQL Score p=0.16 D 3.0 LPR 2.5 Non-LPR Off Me dic a On tion 0.5 Me dic atio n Follow-Up (Years) 4 10 Off M ed On ica tion Me dic a 0.5 tio n Follow-Up (Years) Greenhouse-Geisser correction BMI Subsets GreenhouseGeisser correction 32

33 Failed LNF vs. GERD GreenhouseGeisser correction RF LPR Specific Study Results Extra-Esophageal related GERD: GAO et al (2011) 505 patients with respiratory presentations of GERD Symptom scores were significantly improved at 5 years Mean heartburn score decreased from 5.31 to 1.79; Mean regurgitation score decreased to 1.64; Mean cough score decreased from 6.77 to 2.85; Mean wheezing score decreased from 7.83 to 3.07; Mean hoarseness score decreased to 1.81 All significantly improved (P <0.01) 33

34 Esophageal ph Improvement of Gastroesophageal Reflux Symptoms After Radiofrequency Energy: A Randomized, ShamSham-Controlled Trial Douglas A. Corley, Philip Katz, John M. Wo Wo,, Andreas Stefan, Marco Patti, Richard Rothstein, Michael Kline Rodney Mason, Mason and M. M Michael Wolfe 2003; Kline, Wolfe. Gastroenterology 2003; patients PRIMARY OUTCOMES: OUTCOMES: 6 MONTHS: Active treatment significantly improved heartburn symptom scores, GERD--specific QOL and general QOL vs. sham GERD More active vs. sham patients were without daily heartburn symptoms (61% vs. 33%;; P < % 0.05)) More active vs. sham patients had a >50% improvement in GERD GERD--QOL score (61%vs (61%vs.. 30%; P < )) Sham: No improvement in symptoms at 6 months 12 MONTHS: Active group improvements in symptoms and GERDGERD-HRQL sustained Sham crossover to treatment months: GERDGERD-HRQL significant improvement 34

35 SECONDARY OUTCOMES: OUTCOMES: Daily Medication Use: There there were no differences until a medication-withdrawal protocol medication 6 months PPI use decreased 46% (active) and 29% (sham); active treatment reductions persisted at 12 months Esophageal acid exposure: At 12 months a significant decrease from baseline for all treated patients (both initial active and crossed-over patients No difference at 6 months. There were no perforations or deaths. Radiofrequency Sphincter Treatment Results of MetaMeta-Analysis (Perry 2012) Outcome Variable Studies (n) Patients (n) Mean Follow-up (mo) PreTreatment PostTreatment P-value Subjective Measurements GERD-HRQL QOLRAD SF-36 Physical SF-36 Mental Heartburn Score Satisfaction Score Esophageal Acid Exposure (%ph<4) DeMeester score LES pressure Objective Measurements 35

36 Radiofrequency Sphincter ad o eque cy Sp cte Therapy e apy in Extra--esophageal Reflux Extra LPR Pre-RF Treatment 36

37 Laryngoscopy Pre and Post RF Tx LPR 2 Months Post-RF Treatment 37

38 GERD--Based Sleep Apnea GERD Post RF Tx GERD GERD--Based Sleep Apnea 38

39 Transoral Endoscopic Partial Fundoplication Magnetic Sphincter Augmentation Ganz, et, al. NEJM

40 LES (Internal) Stimulation System Therapy Comparison Outcome Variable RF Tx TIF TAF MSA 1-4 years 12 month 1 year 3 year LES Endo Stimulation 12 month GERDHRQL 26.11/9.2 5 P< % d d reduced regurg 14.9/9.0 P< 001 P< /2.0 P< 0001 P< /2.0 P< 0001 P<.0001 Heartburn Score 3.55/1.19 P< /0.5 P< /7/2 P< /2.0 P<.0001 NA % off PPI s 75% P< % P= % P= % P< % Acid Exposure (%ph<4) 10.2/6.51 P< /6.4 P< /7.3 P< /3.2 P< /3.3 P<.001 DeMeester score 44.4/28.5 P< /23.9 P<.001 NA 30.1/ /11.7 P<.001 P<.001 LES pressure 16.5/20.2 P<.03 NA 9.85/11.1 NA NS P=.43 Nissen Subjective Objective 17.6/23 NS 40

41 Patient Selection The Who. Sphincter -Targeted Therapy Contraindications Subjects j under the age g of 18? Pregnant women Patients without a diagnosis of GERD Hiatal hernia > 3 cm Achalasia Severe scleroderma Esophageal or Gastric Varices Poor surgical candidate 41

42 Hiatal Hernia RF Tx TIF MUSE Linx Endostim Nissen <3 cm <2 cm <3 cm <3 cm <3 cm No limit 45 min 1 hour + 1 day + 1 day 1 hour + 1 day 1 hour + 1 day 45 min Outpatient Patient Selectio Selection n Procedure time 20 min Outpatient Esophagitis p g A, B, C, D A, B A, B A, B A, B, C A, B, C, D Barrett s Reversal Yes No No No No Yes Gastroparesis Correction Yes No No No No Yes BMI All <35 >21 35< <35 <35 All Post Obesity Surgery Yes No No No No No LPR Yes No No No No Yes Repeatable Yes No No Yes Yes Yes Anesthesia Moderate Sedation Genera General l General General General Is It Safe Yet? 42

43 Safety and Tolerability SAE s RF Energy Stimulation Magnetic Sphincter Augment Transoral Anterior Fundo LES Stimulation Transoral Incisionless Fundo P f i Perforation Erosions/ Tears % 0 2 Dysphagia % dilations 0 Explants NA NA 56 (3.4%) 0 2 Stricture Abscess Overall % <0.02% 4/20, % 68/16,000??? Approach to the Patient? Targeted Strategies Based on Pathophysiology, Natural History, and Response to Treatment 43

44 Sphincter--Targeted Treatment Algorithm Sphincter Standard Step tep--up Surgical Medications RF Therapy (PPIs) Internal LES Targeted External LES Targeted vs. Anti-Reflux Surgery Respond to Short Term Medication Poor Response or Long Term Medication Requirement Failed Internal LES Therapy or >3cm Hiatal Hernia Mild GERD symptoms Mild to moderate GERD Functioning LES <3 cm hiatal hernia Highly motivated patient Non-compliant to PPIs Compliant to routine Post Barrett s Ablation Transoral Partial Fundoplication Implanted Devices Magnetic Sphincter Augmentation Implanted Stimulator Intolerant to PPIs Not requiring daily long-term use Post P t bariatric b i t i surgery Tolerant of medication No side effects No drug interactions Post anti-reflux surgery with GERD symptoms Extra-esophageal symptoms of GERD Failed External LES Tx Nissen Fundoplication...Endoscopic therapy back in the game. future success in treatment of patients i h GERD symptoms depends d d on with appropriate sub-classification of this heterogeneous disease, with targeted strategies based on pathophysiology, natural history, and response to treatment. PRATEEK SHARMA and PHILIP KATZ Gastroenterology Feb

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