ENDOLUMINAL THERAPIES FOR GERD University of Colorado Department of Surgery Grand Rounds March 31st, 2008
Overview GERD Healthcare significance Definitions Treatment objectives Endoscopic options Plication Thermal Implants Data on available techniques Applications Conclusions
GERD Healthcare cost U.S. 19 Million cases / year Total cost $9.8 Billion Medication cost $5.8 Billion Rothstein, J Clin Gastroenterol 2008
LES complex GEJ Antireflux Barrier Adequate length / pressure 2cm / 6-26mmHg Radial symmetry Other Factors Motility of esophagus Inadequate clearance Motility of stomach Poor gastric emptying LES Tone Neurotransmitters Hormones / Peptides Sabiston Textbook of Surgery, 18th ed.
Diagnosis / Treatment Subjective Symptoms Heartburn, regurgitation, dysphagia Nonspecific Correlation with objective findings? Objective Findings Abnormal ph or manometry Esophagitis, stricture Barrett s GERD 10% Barrett s 1% CA Treatment Sabiston Textbook of Surgery, 18th ed
Endoscopic Treatment The Endoscopic Niche Outpatient Less invasive Bridge therapy Dr. Rothstein Dr. Swain
The good, the bad, and the ugly Plication 1. EndoCinch 2. NDO Plicator 3. Syntheon ARD EndoGastric Solutions EFS Medigus antireflux system Radiofrequency Stretta (not available) Implants / Injections 1. Enteryx (notorious failure) 2. Gatekeeper (not available)
BARD EndoCinch March 2000 = 1 st FDA approved Dr. Swain 1980s Partial-thickness gastric plication Mechanism Animal - modest increase LES Declines by 6mo (Kadirkamanahan et al. Gastrointest Endosc 1996) Human - LES 4 6 mmhg 27% normal at 6 mo (Tam et al. Am J Gastroenterol 2004) Nearly 50% were missing plications Torquati et al. Surg Endo (2007) 21:697-706
Initial multicenter trial- Gastrointest Endosc 2001 prospective study, 64 pt, 8 centers, 6 months f/u Treatment success = decrease in heartburn severity score of 50% + reduction in use of antisecretory meds Inclusion Symptomatic GERD (no meds), Antisecretory dependence, and acid reflux by ph monitor Exclusion Dysphagia, Grade 3/4 esophagitis, obesity (BMI>40), hiatus hernia >2cm Results Subjective improvement (heartburn frequency / severity) Decreased use of PPI (62% still required some amount) No statistically significant difference in LES pressure 3-month No change in acid exposure 6-month Significant decrease in acid exposure (still 2x normal) Treatment failures? Plication degradation or suture failure
2005 Multicenter trial, 85 pt Endpoints- GERD scores + elimination or reduction in PPI Allowed- failed surgery, hiatal hernia>2cm, Barrett s esophagus Heartburn reduction 59% - 12 mo 52% - 24 mo PPI use decreased Durability? No repeat endoscopy No data > 24 months
Acid Exposure Torquati, et al. Surg Endosc 2007
NDO Plicator Procedure Full Thickness Suture based implant Tightening of LES Lengthening of LES Rothstein, J Clin Gastroenterol 2008
NDO Plicator Pleskow et al (Gastrointest Endosc 2005) NRPT, multicenter N = 64, 12 mo F/U 6 months 74% off PPI Improved Acid exposure (80%) GERD scores 12 mo 68% off PPI Adverse Events Pharyngitis (41%), abdominal pain (20%), chest pain (17%), GI disorder (17%), dysphagia (11%), nausea (6%) Pnuemothorax Pnuemoperitoneum Gastric perforation Pleskow et al (Surg Endosc 2007) 60% off PPI at 3 years
NDO Sham Rothstein et al. Gastroenterology, 2006 RCT,159 pt (78 plication / 81 sham) Primary endpoint: >50% improvement in GERD-HRQL scores Exclusion- severe esophagitis, hiatal hernia >2cm 3 month Plicator improved GERD-HRQL (56%) vs. (19%) sham Decreased PPI Improved acid exposure in plicator vs. sham But subgroup analysis 50% plicator group / 75% sham group - PPIs to maintain GERD symptom control No effect on esophagitis Improved GERD-HRQL scores had disconnect with acid exposure No difference in LES pressures after plication
Summary Objective Changes Decrease in ph exposure? Only a minority of patients Change on LES pressures? Minimal AGA official statement on endoscopic therapy The effect of all techniques to date on LES pressure and 24-hour acid exposure measures is modest, at best normalization of acid exposure is the exception rather than the rule for all of these techniques. Gastroenterology 2006; 131:1313
Summary Patient Application Symptom control Long term durability questionable Limited application Milder GERD cases Limited evidence on patients with: High-grade esophagitis Larger hiatal hernias Atypical manifestations of GERD Failure of PPI Those with strictures/barrett s Sham Significant response to sham treatment Need for larger, randomized, controlled trials
Conclusions Develop / improvements continue at staggering rate Newer devices and techniques may yield better outcomes current data suggest that there are no definite indications for endoscopic therapy for GERD at this time. Both practitioners and patients need to be aware of the limitations in the evidence that exist with these devices at present. Evidence Gastroenterology 2006; 131:1313 Endoluminal therapy