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Modern Approach to the Patient with GERD from a Surgeons Perspective

Matthew Fabian D.O. FACS

Takeaways• Gastroesophageal Reflux Disease is due to a failure of the lower esophageal

sphincter• Gastroesophageal Reflux Disease is usually a progressive disease• Proton Pump Inhibitors

• alleviate symptoms of Gastroesophageal Reflux Disease (About 70%) of the time• do not reduce gastroesophageal reflux• do not reduce risk of esophageal adenocarcinoma• may have side effects with long term use

• Surgery for gastroesophageal reflux disease is indicated for patients with objective evidence of significant reflux (abnormal esophageal pH monitor, Barrett's esophagus, or erosions noted on endoscopy) and:• dependent on PPI for symptom control or• PPI not providing adequate relief

GERD: A Big and Growing Challenge

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1. http://www.aboutgerd.org/introduction-to-gerd.html2. Shah, Nigam H., et al. “Proton pump inhibitor usage and the risk of

myocardial infarction in the general population.” PLoS One 10.6 (2015):e0124653.

3. https://www.eurekalert.org/pub_releases/2008-05/aga-n4p051408.php4. www.ASGE.org5. http://borland-groover.com/gi-education/articles/heartburn-gerd/

LIN X is n o t in te n d e d to tre at, cu re , p re ve n t, m itigate o r d iagn o se can ce r o r B arre tt’s e so p h agu s.

What Causes Reflux Disease?

§ A weak sphincter allows reflux of harmful gastric juice into esophagus

§ Gastric reflux may induce injuries ranging from inflammation to ulceration to cancer

§ Symptoms can be debilitating

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Esophageal Sphincter

Pathophysiology of GERD

§ Physiological GER

• Cleared by peristalsis and salivary production

• Valve mechanism between esophagus and stomach

‒Lower Esophageal sphincter

‒Diaphragm‒His angle

‒Abdomen-Thoracic pressure gradient‒Intra Abdominal esophagus

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Pathophysiology of GERD

§ GastroEsophageal Reflux Disease

• Disruption of the above factors due to:‒Structural Failure of the Lower Esophageal Sphincter

‒Inflammation inhibiting peristalsis‒Over distention or dilation of the stomach‒Gastric hypersecretion

‒Delayed gastric emptying‒Decreased saliva

‒Esophageal motility disorder‒Aerophagia‒Gluttony

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Initial Treatment Options:

§PPI§H2 blockers§Antacids, Tums, etc. §Lifestyle modification

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PPI: FDA approved indications and duration

§ Healing of erosive esophagitis

§ Maintenance of healed erosive esophagitis

§ Symptomatic gastroesophageal reflux disease

• 4-8 weeks. Controlled Studies do not extend beyond 12 months.

§ Eradication of H. pylori

§ Prevention of NSAID induced gastric ulcers

§ Treatment of NSAID induced gastric ulcers

§ Healing of gastric or duodenal ulcer

§ Maintenance of duodenal ulcer

§ Treatment of pathological hypersecretory conditions

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PPI adverse reactions

§Headache§Abdominal pain§Nausea§Diarrhea

§Flatulence

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PPI Precautions

§ Avoid concomitant use of omeprazole with clopidogrel (reduces pharmacological activity of clopidogrel)

§ Atrophic gastritis

§ C. difficile associated diarrhea

§ Bone Fracture

§ Hypomagnesemia

§ Concomitant use of antiretrovirals such as atazanavir and nelfinavir with omeprazole is not recommended.

§ ? Dementia

§ ? Myocardial Infarction

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Medications Aren’t Impacting Barrett’s!Myth: PPIs Prevent Barrett’s??

5 year follow-up on 2481 patients with GERD

10% Progression to a Pre-Cancerous Lesion ON Treatment is Not a Treatment!

Pro GERD Study. P. Malfertheiner et al. Aliment Pharmacol Ther 2012; 35; 154

Maintenance proton pump inhibition therapy and risk of oesophageal cancerNele Brusselaers, Lars Engstrand, Jesper Lagergren

Cancer Epidemiology 53 (Feb 2018) 172-177

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Maintenance proton pump inhibition therapy and risk of oesophageal cancer

• An increased risk of oesophageal cancer was found among all PPI maintenance users

• PPI Increases Risk of Esophageal Cancer by:– Direct Carcinogenic Effect– Bile Salt Toxicity because of the Increased pH in the Stomach– Disruption of the Gastro-Intestinal Microbiome

• Increase of Bacteria that Produce Nitrosamines

• Long term use of PPI should be addressed with caution.

Cancer Epidemiology 53 (Feb 2018) 172-177

Goal of Reflux Surgery: Restore the Reflux Barrier

Restore the Reflux Barrier to Prevent Reflux…without creating Undue Side Effects

§ Resolve symptoms

§ Control regurgitation

§ Improve QOL

§ Reduce dependence on medication

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Traditional Treatment Continuum Leaves A Significant Clinical Unmet Need

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• 20M+ on PPI1

• 38% symptomatic2

• Concern about long-term risks• Costly to patient

• < 1% of symptomatic patients• Concerns: durability, lack of

reproducibility, side effects• Bad reputation with patients

and GIs

1. Shah, N igam H., et al. “Proton pum p inhib itor usage and the risk of m yocardial in farction in the genera l population.” PLoS O ne 10.6 (2015):

e0124653.

2. https://w w w .eurekalert.org/pub_releases/2008-05/aga-n4p051408.php

*Nexium is a registered trademark for Astra Zeneca

Medications are Designed to Address Acid, NOT the Reflux Barrier

§ Patients reflux the same amount ON or OFFmedications

§ Medications designed to address the symptoms of GERD

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F razzon i M , e t a l. R eflux patte rns in patien ts w ith short-segm ent B arre tt's oesophagus: a s tudy us ing im pedance-pH m onito ring o ff and on

pro ton pum p inh ib ito r therapy. A lim entary P harm aco logy & Therapeutics . 30(5):508-15, 2009 S ep 1 .

Median number of refluxes off and on PPI therapy

PPIs Deliver Minimal Therapeutic Gain for Regurgitation and EES

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0% 25% 50% 75%

Chronic cough (improved)

100%

Esophagitis healingMild

Severe

Heartburn reliefEsophagitis

NERD

Regurgitation relief

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

Hoarseness (improved)GERD (-)

Placebo Therapeutic gain

Kahrilas, Peter J., Guy Boeckxstaens, and Andre JPM Smout. "Management of the patient with incomplete response to PPI therapy." Best Practice & Research Clinical Gastroenterology 27.3 (2013): 401-414.;

Traditional Reflux Surgery has Limitations

Nissen Fundoplication§ Key steps:

• Short gastric vessels are divided

• Crural dissection

• Closure of the hiatus

• Upper portion of stomach wrapped around the LES and sutured in place

§ Limitations:

• Inconsistent outcomes (highly surgeon-dependent)

• Permanent anatomical alteration

• Side effects (lim ited ability to belch/vomit);

gas bloat

• Questions about durability

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Creates a one-way valvewhere any rise in gastric

pressure causes the wrapped stomach to clamp down on esophagus to stop

reflux

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Traditional Reflux Surgery has Limitations

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V akil, N im ish, M ichae l S haw , and R usse ll K irby. "C lin ica l e ffectiveness o f laparoscop ic fundop lica tion in a U S com m unity ." The A m erican journa l o f m edic ine 114.1 (2003): 1 -5 .

§ 32% Restarted Acid Suppression Therapy

§ 67% Reported New Symptoms

§ 61% Completely Satisfied

Study assessed clinical effectiveness of LNF in the community

N = 80; mean follow-up 20+/-10 monthsNew Symptoms

SatisfactionC om p let el yS at isf i ed

S om ew h atS at isf i ed

S om ew h atD is sat is fi ed

V er yD is sat is fi ed

LINX is Redefining Reflux Surgery

§ Creates a New “Sphincter”

§ One Way Valve

§ Disrupts Native Anatomy

§ Supraphysiologic

§ “Irreversible” procedure

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§ Augment the Weak LES

§ Increases LES Yield Pressure

§ Preserves Native Anatomy

§ Physiologic

§ Removable

Nissen LINX*

* Data on file

Indication for Use

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FDA Indication For Use:

“The LINX® Reflux Management System is a

laparoscopic, fundic-sparing anti-reflux

procedure indicated for patients diagnosed

with Gastroesophageal Reflux Disease

(GERD) as defined by abnormal pH testing,

and who are seeking an alternative to continuous acid suppression therapy (i.e.

proton-pump inhibitors or equivalent) in the

management of their GERD.”*

*P100049

Design allows augmentation without compression of esophagus

Mechanism of Action – Dynamic Augmentation

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Interlinked Titanium Beads allow dynamic opening

Magnetic Cores provide augmentation (15-25 mmHG*)

G anz, R obert A ., e t a l. "E sophagea l sph incter dev ice fo r gastroesophagea l re flux d isease." N ew E ng land Journa l o f M edic ine 368.8 (2013):

719-727.* D ata on F ile

LINX: A Highly Reproducible Reflux Procedure

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Minimally invasive,

laparoscopic procedure

Out-patient* Normal Diet Post-opSafe1

Allows for restoration of

the reflux barrier

1 L ipham , J . C ., e t a l. "S afe ty ana lys is o f firs t 1000 patien ts trea ted w ith m agnetic sph incter augm enta tion fo r gastroesophagea l re flux

d isease." D iseases o f the E sophagus 28.4 (2015): 305-311.

*A s reported by L IN X prov iders

LINX Extensive Peer-Reviewed Literature

§ Over 100 Peer Reviewed Publications

§ Two FDA 5-year studies completed

§ Long term efficacy and safety validated (11 years)

§ Propensity studies show preferable outcomes to Nissen fundoplication

§ Real-world commercial outcomes exceed pre-approval trial results

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Patient Benefits Sustained to Five Years

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G anz, R obert A ., e t a l. "Long-term outcom es o f pa tien ts rece iv ing a m agnetic sph incter augm enta tion dev ice fo r gastroesophagea l re flux ." C lin ica l G astroentero logy and H epato logy 14.5 (2016): 671-677.

LINX Addresses the Side Effects of GERD

Difficu l tyS wa llo win g

B loa tin g/ Ga ssy Dia rrh ea C o ns tip atio nNa u se a /Vo mitin g

B a se lin e 5 5 2 9 1 8 1 2

LIN X Y ea r 5 6 .0 8 .3 2 .4 6 2 .4

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 00

% o

f Pat

ient

s

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G anz, R obert A ., e t a l. "Long-term outcom es o f pa tien ts rece iv ing a m agnetic sph incter augm enta tion dev ice fo r gastroesophagea l re flux ." C lin ica l G astroentero logy and H epato logy 14.5 (2016): 671-677.

Patients Report Significant and Sustained Improvement in QOL After Treatment with LINX

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OFFProton-Pump Inhibitors

at Baseline

ONProton-Pump Inhibitors

at Baseline

5 Years AfterSphincter

Augmentation

G anz, R obert A ., e t a l. "Long-term outcom es o f pa tien ts rece iv ing a m agnetic sph incter augm enta tion dev ice fo r gastroesophagea l re flux ." C lin ica l G astroentero logy and H epato logy 14.5 (2016): 671-677.

Benefits of LINX Consistently Demonstrated Across Studies

0

5

10

15

20

25

30

Pre- LIN X Post -L INX

GERD-HRQL Score

Saino et al . (5 Yr ) G anz et a l . ( 5 Y r) Bonav ina et a l . (3 Yr)

Rieg ler e t a l. (1 Yr ) Rey nolds et a l . (1 Yr) Louie et a l . (6M )

Sm i th et al . (6M ) Warren et a l . (1 Yr)

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Benefits of LINX Consistently Demonstrated Across Studies

0

10

20

30

40

50

60

70

Pre- LIN X Post -L INX

Moderate/Severe Regurgitation(% of Patients)

G anz et a l . ( 5 Y r) Bonav ina et a l . (3 Yr) Rieg ler e t a l. (1 Yr )

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Benefits of LINX Consistently Demonstrated Across Studies

0

20

40

60

80

10 0

Pre- LIN X Post -L INX

PPI Use (% of Patients)

Saino et al . (5 Yr ) G anz et a l . ( 5 Y r) Bonav ina et a l . (3 Yr)

Rieg ler e t a l. (1 Yr ) Rey nolds et a l . (1 Yr) Louie et a l . (6M )

Sm i th et al . (6M ) Warren et a l . (1 Yr)

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Summary of LINX Safety

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Safety Experience – 3,283 US Patients

Occurrence Rate

Device Removal 2.7%

Perioperative Complications 0.0%

Device Erosion 0.15%

Device Migration 0.0%

Device Malfunction 0.0%

S m ith , C . D an ie l, e t. a l.; Low er E sophagea l S ph incter A ugm enta tion fo r G E R D : The S afe ty o f a M odern Im plant; Journa l o f

Laparoendoscop ic & A dvanced S urg ica l Techn iques (2017)

Conclusion: With a low rate of device removals, rare occurrence of erosions

and benign presentation and management, the clinical evidence supports

MSAD as safe for the widespread treatment of GERD.

Results

Decline of removals overtime

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S m ith , C . D an ie l, e t. a l.; Low er E sophagea l S ph incter A ugm enta tion fo r G E R D : The S afe ty o f a M odern Im plant; Journa l o f Laparoendoscop ic & A dvanced S urg ica l Techn iques (2017)

Identifying the LINX Patient

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• Abnormal pH• BID PPI• SymptomaticØ RegurgitationAbnormal pH

Medication DependentSymptomatic

Barrier Failure

LINX is indicated for patients diagnosed w ith Gastroesophageal Reflux Disease (GERD) as defined by abnorm al pH testing, and w ho are seeking an

alternative to continuous acid suppression therapy (i.e. proton-pum p inhibitors or equivalent) in the m anagem ent of their GERD.

LINX Offers Unique and Important Benefits to Patients and Physicians

§ Reproducible, minimally invasive procedure

§ Consistent results in symptom improvement across multiple studies

§ Significantly reduced PPI dependence9

§ Sustained improvement in HRQL at 5 years

§ Requires no permanent anatomic alteration

• Allows for restoration of the reflux barrier

• Preserves physiologic function (belch and vomit)

• Removable and preserves future treatment options

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G anz, R obert A ., e t a l. "Long-term outcom es o f pa tien ts rece iv ing a m agnetic sph incter augm enta tion dev ice fo r gastroesophagea l re flux ." C lin ica l G astroentero logy and H epato logy 14.5 (2016): 671-677.

Additional Information

Collaborating to Offer LINX

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Identifying Patients

Diagnostic Testing

LINXReferral

Procedure

Early Post-Op Management

Long Term Patient Care

LINX Implanting Surgeon

Referring Physician

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LINX vs Nissen Fundoplication

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LINX offers a more favorable side effect profile vs. fundoplication.

R eynolds, J. L., Zehetner, J., W u, P. , Shah, S ., B ildzukew icz, N . and Lipham , J. C ., Laparoscopic M agnetic Sphincter Augm entation vs.

Laparoscopic N issen Fundoplication: Am erican College of Surgeons (2015), doi: 10.1016/j.jam collsurg.2015.02.025.

EfficacyLNF

baseline 1 yearG E R D H R Q L 18 .8

1 year

4.3

O ff PPI’s 91 .5%

Side EffectsS evere gas b loa t 10 .6%

Inab ility to be lch 25 .5%

Inab ility to vom it 21 .3%

D ysphag ia 12 .8%MAT

CH

ED-P

AIR

ANA

LYSI

S

LINXbaseline 1 year

19.7 4 .2

83 .0%

1 year0

8 .5%

4.3%

10.6%

Reasons for Device Removal

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Reason Total <1 Year 1-2 Years >2 Years Overall rate

Dysphagia 52 37 12 3 1.6%

GERD 19 6 9 4 0.6%Abdominal Pain 4 2 1 1 0.1%Erosion 5 1 3 1 0.15%

Other 5 4 1 0 0.15%

Subsequent MRI 3 0 1 2 0.09%

Vomiting 1 1 0 0 0.03%TOTAL 89 51 27 11 2.7%

Smith C. Daniel, Ganz Robert A., Lipham John C., Bell Reginald C., and Rattner David W.. Journal of Laparoendoscopic & Advanced Surgical Techniques. April 2017, ahead of print. doi:10.1089/lap.2017.0025

Erosions

§ Based upon the limited number of erosions experienced, erosions appear to be:

• Rare, easy to diagnose and electively managed, with no permanent impairment or disability

• Presentation – typically late (greater than 1 year) onset dysphagia/odynophagia

• Diagnosis – EGD with visualization of beads inside lumen of esophagus

• Management- 3 methods all non-emergent/elective procedures‒Single Procedure - Entirely endoscopic after cutting with endoscopic loop

cutter‒Single Procedure - Combined endoscopic and laparoscopic‒Two Separate Procedures

§ Endoscopic after cutting wires of device and removing eroded portion

§ Laparoscopic removal of balance of device after at least one month for healing the mucosa

• Outcomes - No permanent disability or impairment observed

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Smith C. Daniel, Ganz Robert A., Lipham John C., Bell Reginald C., and Rattner David W.. Journal of Laparoendoscopic & Advanced Surgical Techniques. April 2017, ahead of print. doi:10.1089/lap.2017.0025

LINX Work-Up

§ Endoscopy- Confirm esophageal health

§ pH- Validate diagnosis of GERD

§ Manometry- Confirm normal swallow function

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02468

1012

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B L 1 Y R 2 Y R S 3 Y R S 4 Y R S

RECURRENT COUGH(% patients reporting)

Improvement of Extra-Esophageal Symptoms*

B L 1 Y R 2 Y R S 3 Y R S 4 Y R S

NOCTURNAL COUGH(% patients reporting)

B L 1 Y R 2 Y R S 3 Y R S 4 Y R S

ASTHMA(% patients reporting)

B L 1 Y R 2 Y R S 3 Y R S 4 Y R S

CHANGE OF VOICE(% patients reporting)

US Pivotal Data on file

5 Y R S 5 Y R S

5 Y R S 5 Y R S

Doc No 5845 Rev. 5*LINX is not intended to diagnose, treat, cure, prevent or mitigate these symptoms.

Setting Post-op Expectations

§ Pain is very common immediately following surgery and is usually the worst during the first two days. It is very common to have pain or swelling near the esophagus. Some patients will have temporary spasming in their esophagus which causes pain while eating.

§ It is normal and expected to have some level of discomfort or difficulty swallowing (dysphagia) following LINX Surgery. It will normally begin seven to ten days after surgery and slightly increase peaking at the six week mark. Then it will gradually resolve subsiding greatly after twelve weeks following your surgery.

§ The best way to lessen the duration and intensity of dysphagia after LINX surgery is by eating solid foods frequently. Patients will begin eating solid foods the day after surgery or as advised by the surgeon.

• Very important that the patient “exercise” their device and not go on a liquid diet.

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RCT: Linx vs. PPI for Regurgitation/GERD…152 pt Randomized to Linx or BID PPI

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Gastrointest Endosc. 2019 Jan;89(1):14-22

Other Surgical Therapies

§EndoStim-Investigional§Stretta-not recommended§Transoral Incisionless Fundoplication

• Not recommended

§Gastric Bypass

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Takeaways• Gastroesophageal Reflux Disease is due to a failure of the lower esophageal

sphincter• Gastroesophageal Reflux Disease is usually a progressive disease• Proton Pump Inhibitors

• alleviate symptoms of Gastroesophageal Reflux Disease (About 70%) of the time• do not reduce gastroesophageal reflux• do not reduce risk of esophageal adenocarcinoma• may have side effects with long term use

• Surgery for gastroesophageal reflux disease is indicated for patients with objective evidence of significant reflux (abnormal esophageal pH monitor, Barrett's esophagus, or erosions noted on endoscopy) and:• dependent on PPI for symptom control or• PPI not providing adequate relief