Endoscopic Treatment of GERD Gary “Taavi” Reiss. MD, MPH, MBA, FACG

Metropolitan Gastroenterology Associates

LSU Health Sciences Center, Gastroentology

Why do we care about GERD?

Assumptions

GERD is no longer a

problem

Anti-reflux devices have

“flopped” and are no

longer on the market

Data supporting

endoscopic treatment is

limited

This sort of stuff isn’t done

here

Reality

Many patients have an

incomplete response to

medication

Endoscopic treatment is readily available

Data are reasonably

robust

This sort of stuff can be

done anywhere

GERD and PPI response

If you do well with a PPI, you will continue to do

well

Remission rates for PPI and Nissen fundoplication

equivalent five years out, with data trending

towards PPI trumping surgery

LOTUS trial, JAMA 2011;1969-1977.

30%-60% do not achieve complete remission; 28%

of these will not have reflux (normal acid and bile

exposure, normal EGD)

You will NEVER know if you don’t ask. Most of us

don’t ask.

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 end-point 7 placebo controlled trials

Therapeutic gain = 17%

Kahrilas, Howden & Hughes, Am J Gastroenterol 2011; 106: 1419-1425.

GERD: So Simple, So Complex

Refractory Reflux: z/pH

57% 35%

8%

Refractory HB on BID

PPI

Functional Heartburn

Weakly Acidic Reflux

Acidic Reflux

Most patients are

functional

Functional HB dx

requires pH testing

(Rome IV)

Hypersensitive

esopahgus dx requires

pH testing (Rome IV)

Significant minority with

weakly acidic reflux

Mainie I et al. Gut, 2006; 55:1398-1402

Compliance / Patient

Perception Timing

50% of GERD patients are using PPI’s ‘on-demand’ after 4 weeks

70% of GERD patients are using PPI’s ‘on-demand’ after 3 months

15-20% of all medications refilled as indicated

~ 40% patients take > 1 hour before meals

~ 30% patients take AFTER meals

Concerns

Dementia

Cardiac disease

Infection

Osteopenia/osteoporosis

Kidney disease

Intolerance (diarrhea, headache)

www.nexiumlawsuit.com

Hershcovici T and Fass R Dis Esoph 2013;26:27-36

Gunaratnam et al. Aliment Pharmacol Ther 2006;23(10):1473-1477

Why do we care about GERD?

Assumptions

GERD is no longer a

problem

Anti-reflux devices have

“flopped” and are no

longer on the market

Data supporting

endoscopic treatment is

limited

This sort of stuff isn’t done

here

Reality

Many patients have an

incomplete response to

medication or do not take

medication (or will not)

Endoscopic treatment is

readily available

Data are reasonably robust

This sort of stuff can be

done anywhere

GERD Endoscopic Treatment

Options

DEVICE COMPANY Initiation Status 2017

Stretta Curon,

Mederi

2001, 2008 Active use

Endocinch Bard 2000 Discontinued

Enteryx Boston Sci 2005 Voluntary recall, 2005

Gatekeep

er

Medtronic 2004 Development halted,

2005

NDO

Plicator

NDO

Surgical

2005 Bankrupt 2008

MUSE Medigus 2015 Active

TIF/Esophy

X

Endogastri

c Solutions

2007 Active

Endostim Endostim 2009 In development

Available Options

Stretta

EsophyX / TIF 2.0

MUSE

Why do we care about GERD?

Assumptions

GERD is no longer a

problem

Anti-reflux devices have

“flopped” and are no

longer on the market

Data supporting

endoscopic treatment is

limited

This sort of stuff isn’t done

here

Reality

Many patients have an

incomplete response

Endoscopic treatment is

readily available

Data are reasonably

robust

This sort of stuff can be

done anywhere

Low power RF energy

delivered to tissue

“Stretta therapy remodels the musculature of the lower esophageal sphincter

(LES) and gastric cardia. Clinical studies demonstrate that the Stretta RF

treatment results in significant reductions in tissue compliance and

transient LES relaxations. These mechanisms act to restore the natural

barrier function of the LES as well as to significantly reduce spontaneous

regurgitation caused by transient inappropriate relaxations of the sphincter.”

Edward D. Auyang, Patrice Carter, Thomas Rauth, Robert D. Fanelli,

SAGES Guidelines Committee, Endoluminal Treatments for GERD, May 2013

Multi-level treatment remodels

LES and Gastric Cardia

Function improved, reduced

compliance, fewer TLESRs

Stretta - Procedure

Herman et al,

Published Online

Colorectal Disease

December 2014

Demonstrating a thinner

muscularis propria in

the Untreated group,

compared to thicker

in the RF group.

UNTREATED RF

Herman et al,

Poster DDW 2013

Growth in smooth

muscle cells

14

Increase in thickness of the GE

junction – muscularis propria

Baseline control-

untreated

7 months

post-treatment

Kim M, GI Endoscopy 2003

Increased Thickness CANINES

De Angelis C, Repici A, Dughera L. UEGW 2004

Before Stretta

After Stretta 3 Months

HUMANS

INFLUENCE ON TLESR’S

A six month follow up on 20 patients

Corley et al. Gastroenterology 2003

Mechanism

Data Sample

Reduction in esophageal acid exposure

• Perry et al. 2012 – Surg Lap, Endo & Perc Tech

• Aziz et al 2010 – Curr Opin Gastroenterol - RCT

• Arts et al 2007 – Digestive Disease Science

• Mattar et al. 2006 – Surg Endosc

• Lufti et al. 2005 – Surg Endosc

• Cipoletta et al. 2005 – Surg Endosc

• Torquati et al. 2004 – Surg Endosc

• Triadafilopoulos et al. 2004 – Surg Endosc

• Houston et al. 2003 – Surg Endosc

• Richards et al. 2003 – Annals of Surgery

• Triadafilopoulos et al. 2002 – Gastrointest Endosc

• Corley et al. 2003 – Gastroenterology - RCT

Reduction in transient LES relaxations

• Arts et al. 2012 – Am Journal of Gastroenterol - RCT

• Tam et al. 2003 – Gut

• Kim et al. 2003 – Gastrointestinal Endosc

Decreased tissue compliance without fibrosis

• Arts et al. 2012 – Am Journal of Gastroenterol – RCT

Increase in LES wall thickness

• DiBaise et al. 2002 – Am Journal of Gastroenterol

• Chang et al. 2001 – Gastrointestinal Endosc

• Kim et al. 2003 – Gastrointestinal Endosc

Increased LES pressure

• Aziz et al. 2010 – Curr Opin Gastroenterol

• Meier et al. 2007 – Scandinavian Journal of Gastro

• Tam et al. 2003 – Gut

• Utley et al. 2000 – Gastrointest Endosc

“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. 2003

“Stretta improved GERD symptoms and

decreased GEJ compliance. Decreased

GEJ compliance, which reflects altered

LES neuromuscular function, may

contribute to symptomatic benefit by

decreasing refluxate volume.”

- Arts et al. 2012

“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. 2009

Stretta - Criticism

Small studies

Too much potential for bias (only 4 RCT)

Physiologic data not robust

Too many single study sites

Concern that neuromodulatory effect may play a role

Discordance between timeframe of pH improvement and symptom improvement

Stretta is Safe & Efficacious

Results of Meta-Analysis

Outcome Variable Studies

(n)

Patients

(n)

Mean Follow-

up (mo)

Pre-

Stretta

Post-

Stretta

P-value

Subjective Measurements

GERD-HRQL 9 433 19.8 26.11 9.25 0.0001

QOLRAD 4 250 25.2 3.30 9.25 0.0010

SF-36 Physical 6 299 9.5 36.45 46.12 0.0001

SF-36 Mental 5 264 10.0 46.79 55.16 0.0015

Heartburn Score 9 525 24.1 3.55 1.19 0.0001

Satisfaction Score 5 366 21.9 1..43 4.07 0.0006

Objective Measurements

Esophageal Acid

Exposure (%pH<4)

11 364 11.9 10.29 6.51 0.0003

DeMeester score 7 267 13.1 44.37 28.53 0.0074

LES pressure 7 263 8.7 16.54 20.24 0.0302

•Perry et al. 2012 – Surg Lap, Endo & Perc Tech

Second meta-analysis, 2-4 studies, only RCT

Clinical Gastroenterology and Hepatology 2015 13, 1058-1067.e1DOI: (10.1016/j.cgh.2014.10.013)

A) mean (%) time pH < 4 / day

B) Mean LES pressure

A) Off PPI at end of study

B) HRQOL

No Evidence for Efficacy of Radiofrequency Ablation for

Treatment of Gastroesophageal Reflux Disease: A

Systematic Review and Meta-Analysis

Seth Lipka, Ambuj Kumar, Joel E. Richter

New (Final?) Stretta Meta-Analysis 2017

Systematic Review and Meta-Analysis of Controlled

and Prospective Cohort Efficacy Studies of Endoscopic

Radiofrequency for Treatment of GERD

Ronnie Fass, Frederick Cahn, et al – Surgical Endoscopy Online 02/17

HIGH QUALITY – COMPREHENSIVE STUDY:

• Large size ranks in top 1% of Systematic Review/Meta-Analysis

• 28 Studies, 2468 Patients, up to 10-yrs follow-up (avg 25 months)

SUMMARY OF RESULTS: • Significant improvement in health related quality of life scores

• Significant reduction in heartburn symptom scores • The majority of patients off proton pump inhibitors (PPIs)

• Significant healing of erosive esophagitis

• Significant reduction in esophageal acid exposure • Low adverse event rate of <1%

New (Final?) Stretta Meta-Analysis 2017

OUTCOME MEASURE POOLED RESULTS (P<0.001)

Health Related Quality of Life Score Reduced by -14.6 [-16.48, -12.73]

Medication Use (PPI) Majority (51%) off PPIs at follow-up

Incidence of Erosive Esophagitis Reduced by 24%

Esophageal Acid Exposure Reduced by mean of -3.01 [-3.72, -2.30]

(30% Normalized)

All reached statistical significance

“This comprehensive analysis combined our clinical expertise with Dr. Cahn’s statistical experience to produce the most

thorough and objective review of currently available data. The

results demonstrate that Stretta is a clinically effective and safe

therapy for GERD.”

Ronnie Fass, MD Metro Health Medical Center, Case Western University, Cleveland Ohio

SAGES CSR Guideline Gives Stretta

Strongest Grade Recommendation

ASGE Guidelines: June 2015

ENDOSCOPIC MANAGEMENT OF GERD

• Statements on Stretta: “Adverse events were infrequent and

typically minor. The technique appears to durably relieve GERD

symptoms for up to 10 years in the majority of patients…This

technique uses RF energy delivery to the distal esophagus and

appears to reduce GERD by decreasing tissue compliance and

reducing transient lower esophageal relaxations.”

Summary: Endoscopic antireflux therapy may be

considered for select GERD patients.

Gastrointest Endosc 2015;81:1305–1310 / DOI:

http://dx.doi.org/10.1016/j.gie.2015.02.021

Available Options

Stretta

EsophyX / TIF 2.0

MUSE

MUSE AND TIF: HOW DO WE

RECREATE THE NISSEN?

TIF PROCEDURE

TIF RESTORES ANATOMY / VALVE

Initial Results Disapointing

SAGES Review of TIF

Quality of evidence

(++) low

Recommendation: weak

“Significant untoward events…”

“Results appear mixed…”

“Majority of literature is underpowered…”

ASGE

“Results variable…”

“Lack of routine reporting of pH data…”

“Most studies small, short term follow up…”

“Poorer results with earlier of the device / technique”

Gastrointest Endosc 2015;81:1305–1310 / DOI: http://dx.doi.org/10.1016/j.gie.2015.02.021

Why Such a Poor Initial Showing?

Intent: Mimic Surgery Practice: Learning Curve

Name TLA Fastner Plication Wrap

Endoluminal

fundoplicatio

n

ELF Below z line Gastro -

gastric

No

Transoral

incisionless

fundoplicatio

n

TIF 1 Above z line

1 cm

Esophago-

gastric

No

Transoral

incisionless

fundoplicatio

n

TIF 2 1-3 cm

above z

line; more

length

along

greater

curve

Esophago-

gastric

Yes

RCT: RESPECT TRIAL

TIF 2 SPECIFIC STUDIES

MUSE: Surgical Endostapler

Zacherl J, et al. Surg Endosc 2015;29:220-9

MUSE: Endoscopic Anterior

Fundoplication

Roy-Shapira A et al. Surg Endosc 2015;29:3717-

21

MUSE DATA

37 patients, Uncontrolled, 4 yr

Kim HJ et al. Surg Endosc (2016) 30:3402–3408

MUSE DATA

Kim HJ et al. Surg Endosc (2016) 30:3402–3408

Why do we care about GERD?

Assumptions

GERD is no longer a

problem

Anti-reflux devices have

“flopped” and are no

longer on the market

Data supporting

endoscopic treatment is

limited

This sort of stuff isn’t done

here

Reality

Many patients have an

incomplete response

Endoscopic treatment is

readily available

Data are reasonably

robust

This sort of stuff can be

done anywhere