Minimally Invasive Management of GERD: Are We Ready For Prime Time?

Presented on: September 21st 2015

John E. Pandolfino, MD, MSCIProfessor of Medicine

Feinberg School of Medicine, Northwestern University

Chief, Division of Gastroenterology and Hepatology Northwestern Medicine

Northwestern Memorial Hospital

Vakil N et al. Am J Gastroenterol 2006;101:1900

GERD is a condition which develops when the reflux of stomach content causes troublesome

symptoms and / or complications

Esophageal Syndromes

Extra-esophageal Syndromes

Symptomatic Syndromes

• Typical reflux syndrome

• Reflux chest pain syndrome

Syndromes with Esophageal Injury

• Reflux esophagitis• Reflux stricture• Barrett's esophagus

• Adenocarcinoma

Established Association

• Reflux cough

• Reflux laryngitis

• Reflux asthma

• Reflux dental erosions

Proposed Association

• Sinusitis• Pulmonary

fibrosis• Pharyngitis• Recurrent otitis

media

Primary pathophysiology

EsophagitisSeverity

≈

# of refluxevents X

Tissuesensitivity

Causticity ofgastric juice

XAcidclearance

Determinants of Reflux Severity

SymptomTriggers

≈ Refluxevents

X

Tissuesensitivity

Acidity ofgastric juice

XAcidclearance

Symptommodulators

≈

Not a primary abnormality of GERD

Determinants of Reflux Severity

SymptomTriggers

≈ Refluxevents

X

Tissuesensitivity

Acidity ofgastric juice

XAcidclearance

PPI therapy of GERD is compensatory, not curative

Symptommodulators

≈

Targets of PPI therapy

Determinants of Reflux Severity

PPI efficacy for potential manifestations of GERDEstimates based on available RCT data

PJ Kahrilas 2011RM #46 v4/6/11 PJK

0% 100%25% 50% 75%

Esophagitis healingMild

Severe

Heartburn reliefEsophagitis

NERD

Regurgitation relief

Chest pain (50% relief)GERD (+pH)GERD (-pH)

Hoarseness (improved)GERD (-)

Chronic cough (improved)

Placebo Therapeutic gain

SymptomTriggers

≈ Refluxevents

Tissuesensitivity

X Acidity ofgastric juice

XAcidclearance

Symptommodulators

≈

PPI FailuresAbnormal in number,

composition, or volume refluxed

Determinants of Refractory Reflux

Lateral projectionPA projection

6x6mm

Dimensions and Asymmetry of the EGJ

Pandolfino JE, et al. Gastroenterology 2003;125:1018-24

6 mmHg4 mmHg-2 mmHg 0 mmHg 2 mmHgDistentionpressure

Normal

GERD(-) HH

GERD(+) HH

-4 mmHg

EGJ Distensibility: Target for Therapy

Kwiatek et al. J Gastrointest Surg. 2010 Feb;14(2):268-76

Reflux-symptom Association on PPI TherapyMechanism of PPI failure

168 patients with symptoms

Symptoms 144 (85%)

No symptoms 24 (15%)

Positive SI 69 (48%)

Negative SI 75 (52%) +SI acid

16 (11%)+SI non-acid

53 (37%)

FunctionalAlternative DX Acid

BreakthroughNon-Acid

Reflux

Maine et al. Gut. 2006 Oct;55(10):1398-402

?

Antireflux Surgery in GERDIndications

When antireflux surgery and PPI therapy are judged to offer similar efficacy in a patient with an esophageal GERD syndrome, PPI therapy should be recommended as initial therapy because of superior safety.

I. When a patient with an esophageal GERD syndrome is responsive to, but intolerant of, acid suppressive therapy, antireflux surgery should be recommended as an alternative.

II. Antireflux surgery for patients with an esophageal GERD syndrome with persistent troublesome symptoms, especially troublesome regurgitation, despite PPI therapy.

i. Must have proven GERD.ii. The potential benefits of antireflux surgery should be weighed against the

deleterious effect of new symptoms consequent from surgery, [dysphagia, gas bloat, IBS,].

Endoscopic Therapies for GERDShould have similar indications: If they work

When endoscopic therapies and PPI therapy are judged to offer similar efficacy in a patient with an esophageal GERD syndrome, PPI therapy should be recommended as initial therapy because of superior safety.

I. When a patient with an esophageal GERD syndrome is responsive to, but intolerant of, acid suppressive therapy, endoscopic therapies could be recommended as an alternative.

II. Endoscopic therapies for patients with an esophageal GERD syndrome with persistent troublesome symptoms, especially troublesome regurgitation, despite PPI therapy.

i. Must have proven GERDii. The potential benefits of endoscopic therapies should be weighed

against the deleterious effect of new symptoms consequent from the procedure, [dysphagia, gas bloat, IBS,].

Endoscopic Therapies for GERDGuidelines/Position Statements

AGA GERD Guidelines 2008:The use of currently commercially available endoluminal antireflux procedures in the management of patients with an esophageal syndrome.(Insufficient evidence to recommend)

ACG Guidelines 2013:The usage of current endoscopic therapy or transoral incisionless fundoplication cannot be recommended as an alternative to medical or traditional surgical therapy. (Strong recommendation, moderate level of evidence)

Minimally invasive treatments for GERD A brief history

• Stretta 2001 redesigned and active• EndoCinch 2000 moribund• Enteryx 2005 voluntary recall 2005• Gatekeeper 2004 halted 2005• NDO Plicator 2005 halted 2008• Esophyx (TIF) 2007 active development• Torax (Linx) 2008 active development

First Publication Status 2015

Endoscopic Therapies for GERDStretta

• Technique: Safe and easy to use endoscopic procedure that is performed with minimal complications {< 30 minutes}.- Transient chest pain common

Balloon placement Multiple treatments Remodeling and bulking of the EGJ

Study Mean LESP Mean %AET PPI wd

Stretta Sham Stretta Sham Stretta Sham

Corley (n=64) 16.2 [10.6,23] 18 [14.8,22.5] 9.9[4,14.7] 10.7[5.9,13] 58% 52%

Coron (n=43)* n/a n.a 11.4(+/-6.3) 8.8 (+/-6.1) 15% 0%

Aziz (n=36) 16.2 (+/- 4.5) 15.9 (+/- 3.2) 6.7( +/- 2.8) 8.2 (+/- 3.1) 16% 0%

Arts (n=22) 16.3 (+/- 1.9) 13.3 (+/- 2.0) 15 9 n/a n/a

* This study did not include a sham arm and compared Stretta to PPI and control

Endoscopic Therapies for GERDStretta

• Moderate symptom improvement with ? difference in objective findings.

Endoscopic Therapies for GERDStretta

Conclusions:• Stretta appears to be safe and is the easiest to use.

• Stretta should be considered in proven GERD patients with no hernia who suffer from troublesome regurgitation, belching and cough despite PPI therapy.

Downside:

• Durability

• Lack of true anatomical correction

Endoscopic Therapies for GERDEsophyx

• Technique: Endoscopic procedure that is similar to fundoplication (49 minutes)

Fasteners deployed Device retrieval Valve with serosa-to-serosa approximation

below Z-line

Endoscopic Therapies for GERDEsophyx

P = 0.023

TIF/Placebo Sham/PPI0%

10%20%30%40%50%60%70%80%

67%45%

• RESPECT- Primary endpoint of troublesome regurgitation

Endoscopic Therapies for GERDEsophyx

0

5

10

15

Screening 6-month

p<0.01

TIF/placebo 6-month evaluation group (n=76, PP less 4 EF & 1 lost to f/u)

ULN

%

0

5

10

15

Screening 6-month

p=ns

Sham/PPI 6-month evaluation group (n=28, PP less 9 EF & 1 lost to f/u)

RDQ reflux symptom scores (on medication)

TIF/Placebo (Screening on PPIs) TIF/Placebo (6 months on placebo)0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

Sham/PPIs (Screening on PPIs) Sham/PPI (6 months on PPI)0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

ScreeningTF/placebo

6-monthsTF/placebo

Screeningsham/PPI

6-monthssham/PPI

P < .001 0.6 (0, 1.3)

3.1 (2.4, 3.8)

3.3 (2.5, 4.0)

0.9 (0.1, 2.0) P < .001

TIF/placebo (n=76, PP less 4 EF & 1 lost to f/u)

Sham/PPI (n=28, PP less 9 EF & 1 lost to f/u)

Endoscopic Therapies for GERDEsophyx

Significant adverse events

Adverse event Onset DurationSevere epigastric/abdominal pain Day 1 2 days

Severe chest pain Day 5 2 weeks

Severe musculoskeletal pain Day 5 1 day

Moderate epigastric/abdominal pain Day 1 4 weeks

Moderate dysphagia Day 1 8 days

Mild dysphagia Day 1 1 day

Mild nausea Day 1 1 day

TF/placebo group (n=87)

Severe nausea Day 1 2 days

Sham/omeprazole group (n=42)

Endoscopic Therapies for GERDEsophyx

Endoscopic Therapies for GERDEsophyx

Conclusions:• TF appears to be safe, without fundoplication side

effects.

• TF should be considered in proven GERD patients with small or absent hiatal hernia who suffer from troublesome regurgitation, despite PPI therapy.

Downside:

• Durability

• Ease of use

• Still not helpful in patients without hernia

Minimally Invasive Therapy for GERDLINX

Bonavina L et al. J Gastrointest Surg 2008;12:2133

In position just below Z-line

Lx 11 v2/16/13 PJK Ganz R, et al N Engl J Med 2013;368:719-27

Magnetic sphincter augmentation3 year results of uncontrolled trial

Lx 12 v1/29/14 PJK

PPI use Regurgitation

Esophagitis

Dysphagia

Ganz R, et al N Engl J Med 2013;368:719-27

Magnetic sphincter augmentationPrimary outcome- pH-metry normalization

Lx 13 v1/29/14 PJKGanz R, et al N Engl J Med 2013;368:719-27

Minimally invasive Therapy for GERDLINX

Conclusions:• Appears to be as effective as fundoplication and is

reversible.

• May be reserved for proven GERD patients with and without hernia who require treatment beyond PPI therapy.

Downside

• No sham controlled data yet.

• Still an implant- 3% of 4000 cases have been explanted

EGD and possible reflux testing if EGD (-) and symptoms continue

Define Phenotype-Reflux Testing

Proven Refractory RefluxHernia

Proven Refractory RefluxNormal Anatomy

Consider Intervention*Stretta/Esophyx/LINX?

Consider Intervention*Hernia repair

LINX/ Fundoplication

Not RefluxAlternative Diagnosis*

Neuromodulator

Document Compliance

Consider motility (HRIM) testing for atypical presentationRule out eating disorder/rumination

* R/O major motility disorder, belching syndrome and gastric emptying issue if not done already

Lifestyle modificationsBehavioral Intervention

Optimize medicationsLifestyle modifications

Behavioral Intervention

Optimize medications

Northwestern Refractory GERD ApproachHeartburn, Regurgitation, Chest Pain

Lifestyle modificationsBehavioral Intervention

Stop PPI

Baclofen/Neuromodulator

Thank You