Endoscopic treatment of GERD - LSGE€¦ · TREATMENT OPTIONS FOR GERD Sandhu et al. Gut Liver 2018; 12(1):7-16. GERD MANAGEMENT ALGORITHM Persisting symptoms Suspected GERD. PPI

UPDATE IN ENDOSCOPIC MANAGEMENT OF GERD

Najib AL GHOSSAINI, MDAin Wazein Medical Village

Gastroenterologist

Director Of Endoscopy Unit

LSGE meeting – December 7, 2018

DISCLOSURES-Abbvie: Advisory board-Phenicia: Speaking-Wilson Cook: Support of Scientific activities-Boston Scientific: Support of Scientific activities-FujiFilm: Grant

OUTLINE

-GERD overview-Available solutions:

• Medical treatment + lifestyle modifications• Surgical• Endoscopic

-Description of different endoscopic techniques-Trials / Metaanalyses-Conclusion

GERD – MONTREAL DEFINITION

Vakil et al., Am J Gastroenterol 2006

HeartburnRegurgitatio

nChest pain

EsophagitisStrictureBarrett

GLOBAL DISTRIBUTION OF THE BURDEN OF GERD

El-Serag et al. Gut 2014

27.80%25.90%

7.80%

33.10%

11.60%

23%

North America

Europe East Asia Middle East Australia South America

CLASSIFICATION OF PATIENTS WITH HEARTBURNS – ROME IV

The phenotypes of patients with heartburn based on the Rome IV criteria.

Zhang et al. UEG journal 2018

SELECTING THE RIGHT PATIENT

REFLUX TESTING – LYON CONSENSUS

Endoscopy pH or pH impedance HRM

Conclusive evidence for

pathologic reflux

Borderline for conclusive evidence

Adjunctive for supportive evidence

Evidence against pathologic reflux

LA grades C and D esophagitis

Long segment Barret’s mucosa

Peptic esophageal stricture

AET>6%

LA grades A and B esophagtis AET 4-6%Reflux episodes 40-80

Hypotensive EGJ

Hiatal hernia

Esophageal hypomotility

Reflux symptom association

Reflux episodes > 80

Low MNBI

Low PSPWI

Histopathology (score)

Electron microscopy (DIS)

Low mucosal impedance

AET<4%Refluxepisodes < 40

Gyawali et al. Gut 2018MNBI Mean Nocturnal Baseline Impedance

PSPWI Post-Reflux Swallow-Induced Peristaltic Wave Index HRM high resolujtion manometryAET acid exposure time

ROME IV – OVERLAP GERD / FUNCTIONAL SYMPTOMS

Aziz et al. Gastroenterology 2016

Aziz et al. Gastroenterology 2016

ROME IV – OVERLAP GERD / FUNCTIONAL SYMPTOMS

TREATMENT OPTIONS FOR GERD

Sandhu et al. Gut Liver 2018; 12(1):7-16

GERD MANAGEMENT ALGORITHM

Persisting symptoms

Suspected GERD

PPI therapy

Consider other causes

Endoscopy if risk factors or alarm symptoms

Consider surgery or endoscopic therapy

Endoscopy and24 h pH/impedence metry

on PPI

Double dose PPI

Maintenance therapy

Resolution No improvement

REFRACTORY GERD

10 – 40% do not respond to PPI BID

Crawley et al. J Clin Outcomes Manag 2000; 7:29.Fass et al. J Gastroenterol Hepatol 2012; 27 Suppl 3:3El-Serag et al. Aliment Pharmacol Ther 2010; 32:720

LONG TERM USE OF PPIFDA warnings:

• Clostridium difficile infection,

• Bone fractures,

• Hypomagnesemia,

• Higher incidence of chronic kidney disease in susceptible populations

• Vitamin B12 def

Strand et al. Gut Liver 2017 Jan; 11(1): 27–37

Esophagealhypomotility

SURGICAL FUNDOPLICATION

-surgical fundoplication-Not recommended in patients who do not respond to PPI therapy

-Suggested for patients not responsive to PPIs but with documented reflux on pH-impedance analysis

-Preoperative ambulatory pH monitoring is mandatory in patients withoutevidence of erosive esophagitis. R/O achalasia or scleroderma.

-Surgery is as effective as medical therapy for carefully selected patients with chronic GERD when performed by an experienced surgeon.

Philip O. Katz et al. Am J Gastroenterol 2013; 108:308–328

270°

total

LAPAROSCOPIC FUNDOPLICATIONDRAWBACKS

• 25% of patients restart PPI on long term follow up

• 15-30% of patients need reintervention

• Dysphagia

• Bloating

• Inability to belch

ENDOSCOPIC ANTI-REFLUX TREATMENT

Nabi et al. Clin Endosc 2016

TYPES OF ENDOSCOPIC TREATMENT

Transoral incisionless fundoplication (TIF) using: EsophyX device - 2007 Medigus Ultrasonic Surgical Endostapler (MUSE) - 2015 Endoscopic plication device (GERDx™) - 2018

Radiofrequency energy delivery to lower esophageal sphincter usingSTRETTA device - 2000/updated in 2007

Mucosal resection: Anti-reflux mucosectomy (ARMS) described in 2014

Previously developed endoscopic anti-reflux devices no longer marketedbecause of safety concerns and lack of efficacy: EndoCinch device (CR Bard, Inc, Murray Hill, NJ, USA) Endoscopic Suture device (Wilson-Cook, Winston-Salem, NC, USA) Endoscopic Plication System (Plicator; NDO Surgical, Inc, Mansfield

Mass, USA) Enteryx (Boston Scientific Corp, Boston, Mass, USA)

Rouphael et al. Curr Treat Options Gastroeterol 2018Nabi et al. Clin Endosc 2016

Figure 1

Gastrointestinal Endoscopy 2017 86, 931-948DOI: (10.1016/j.gie.2017.08.001)

EsophyX2 HD device. (A) Tip and (B) control body

(EndoGastric Solutions, Redmond, Washington)

ENDOSCOPIC ANTI-REFLUX DEVICES - TIF

Thosani et al. GIE 2017;86(6),931-948

Figure 3

TIF (transoral incisionless fundoplication) 2.0 procedure

(EsophyX device; EndoGastric Solutions, Redmond, Washington).

ENDOSCOPIC ANTI-REFLUX DEVICES -TIF

Thosani et al. GIE 2017;86(6),931-948

PROCEDURE EVOLUTION

Gerson et al. Chirurgia 2018

Figure 4


ENDOSCOPIC ANTI-REFLUX DEVICES- MUSE

A, MUSE console and (B) tip of the endoscope

(Medigus Ltd, Omer, Israel)Thosani et al. GIE 2017;86(6),931-948

Figure 5


ENDOSCOPIC ANTI-REFLUX DEVICES - MUSE

MUSE procedure. A, retroflexion. B, stapling. C,recreated GE junction

(Medigus Ltd, Omer, Israel)

Thosani et al. GIE 2017;86(6),931-948

Figure 6


ENDOSCOPIC ANTI-REFLUX DEVICES

Stretta catheter (Mederi Therapeutics, Greenwich, Connecticut).

Thosani et al. GIE 2017;86(6),931-948

Figure 7


ENDOSCOPIC ANTI-REFLUX DEVICES

Thosani et al. GIE 2017;86(6),931-948

GERDX

Weitzendorfer et al. Surgical endosc 2018

GERDx™ (G-SURG GmbH, Seeon-Seebruck, Germany)

MUCOSECTOMY(ARMS)

• Semi-circumferential mucosectomy in the gastric cardia

• The artificial ulcer heals with shrinkage and contracture of mucosal defect

• Creation of an artificial flap valve at gastric cardia.

Inoue et al. Gastrointest endosc 2017

COMPARATIVE COST

Thosani et al. GIE 2017

GERD-HRQL SCORE

TIF

INDICATION OF TIF-Patient > 18 y o -GERD that REQUIRES AND RESPONDS TO pharmaceutical therapy-hiatal hernia < 2 cm-BMI < 35

RISK OF TIF PROCEDURE-Sore throat, hoarseness, globus-Temporary dysphagia-Nausea, vomiting-Left shoulder pain from CO2 insufflation-Temporary abdominal pain

Mild adverse reactions in 25% of patientsSerious adverse events in 0.5% of patients

CONTRA-INDICATIONS FOR TIF- Bleeding disorder- Stricture or severe esophagitis- Large hernia > 2 cm- Esophageal varices- Esophageal candidiasis- Less than 18 y o- BMI > 35

RESPECT STUDYRandomized, blinded, sham- and placebo-controlled study

TIF/placebo n=87; SHAM/PPI n=42

Hunter et al. Gastroenterology 2015

1

TEMPOTRIAL

Trad et al. Surgical innovation (2015)

Randomized trial 63 patients-40 TIF-23 PPIFollowed 6 months

2

TEMPO TRIALThe 3 major findings :(a) TIF was more effective than PPIs in elimination of

troublesome regurgitation(b) 90% of TIF patients were completely off PPIs at 6-month (c) TIF was equivalent to PPIs in normalizing distal

Esophageal Acid Exposure

Trad et al. Surgical innovation (2015)

TIF VS. SHAM TO CONTROL CHRONIC GERD Time in clinical remission

after either TIF or sham intervention during the 6 months of follow‐up.

3

44 patients:22 in each arm

Håkansson et al. Aliment Pharmacol Ther. 2015

TIF VS. SHAM TO CONTROL CHRONIC GERD

Total acid exposure in % by pH recordings at baseline and after 6 months post‐therapy in the active intervention group (TIF) and in the sham group.

Håkansson et al. Aliment Pharmacol Ther. 2015

METAANALYSIS OF THE 3 RCT’S

• At 3 years (Comparison to PPI or sham procedure):

- improved esophageal pH- decrease in PPI utilization,- improved quality of life.


METAANALYSIS OF THE 3 RCT’S


MUSE

ENDOSCOPIC FUNDOPLICATIONWITH MUSE™: 6-MONTH RESULTS

- Multi-center prospective trial- 69 patients

At 6 months, 50 % reduction in GERD-HRQL score (off PPI) was achieved in 48 of 66 patients (73%),

-Primary endpoint > 50 % improvement in GERDHRQL score

Zacherl et al. Surg endosc 2015

1

Long-term F/U of GERD treatment withMUSE™ endoscopic stapling device

Efficacy and safety data for 37 patients were analyzed at baseline, 6 months, and 4 years post procedure.

Patients who remained off daily PPI were 83.8 % (31/37) at 6 monthsand 69.4 % (25/36) at 4 years post-procedure.

Kim et al. Surgical endosc 2016

2

STRETTAAdvantages:-under conscious sedation as a day care procedure-duration is short, -safety and efficacy have been studied > 10 y. -Does not prevent subsequent therapy like surgery if required.

Drawbacks :-wide variability in response rates (16% to 86%) -low rate of improvement in objective parameters (acid exposure time)-Complete cessation of PPI in only 40% of patients -Patients with large hiatal hernia and severe esophagitis are not ideal candidates for RFA.

Adverse events:-chest pain (50%), -transient fever,-esophageal ulcers. -Gastroparesis


IMPROVEMENT OF GERD AFTERRADIOFREQUENCY : A RANDOMIZED, SHAM-CONTROLLED TRIAL

Corley et al. Gastroenterology 2003

1

STRETTA - CHANGE IN MEAN GERD HRQL

Significant difference between active and Sham treatment at 6 months (P 0.003)


STRETTA – DECREASE IN PPI USE AT 6 MONTHS


MULTICENTER RANDOMIZED, DOUBLE-BLINDED, CONTROLLEDTRIAL (WITHOUT SHAM PROCEDURE)

2

Coron et al. Alim Pharmacol Ther 2008

STRETTA SINGLE/DOUBLE DOSE VS SHAM

3

Improvement at 12 months:-HRQL scores-LES basal pressure-24-hour pH scores-daily PPI use

In single and double Strettagroups (P < 0.01)

Aziz et al. Surg Endosc 2010

METAANALYSIS OF THE AVAILABLE RCT’S – LIPKA ET AL.-165 patients from 4 RCTs-compared Stretta a sham or to PPI

No difference between the Stretta versus sham groups or Stretta versus PPI groups for:-(%) of time esophageal pH <4 / 24 h-LES pressure-ability to stop PPI therapy -GERD-HRQL

Lipka et al. Clinical Gastroenterol Hepatol 2015

METAANALYSIS OF THE AVAILABLE RCT’S – LIPKA ET AL.


METAANALYSIS OF THE AVAILABLE RCT’S – LIPKA ET AL.


METAANALYSIS OF RCT’S AND COHORT STUDIES- HRQL

Fass et al. Surg Endosc 2017

METAANALYSIS OF RCT’S AND COHORT STUDIES – HEARTBURN SYMPTOM SCORE


METAANALYSIS OF RCT’S AND COHORT STUDIES – RELIANCE ON PPI


RESULTS

• Significant improvement of: • HRQL• heartburn score • erosive esophagitis incidence.

• Significant reduction of:• PPI use • esophageal acid exposure

• No significant effect on LES basal pressure.

• Safety profile is excellent with only 1% AE rate.


GERDX™

GERDX™• Only one study available• Single-arm study• 40 patients included, 30 studied• Results are encouraging but further studies are required• The technique improves the distal acid exposure of the

esophagus, typical reflux-related symptoms and QoL in well-selected patients.

Weitzendorfer et al. Surgical endosc 2018

MUCOSECTOMY

ARMS(SEMI-CIRCUMFERENTIAL MUCOSECTOMY)

• 67 consecutive cases• Symptoms of GERD improved significantly after ARMS• GERD Q score decreased from 9.9 to 5.7 (P<0.01) at 2

months after therapy. • Symptom improvement was kept one year after.• Improvement of pH impedance monitoring from 22.8% to

7.0% (P<0.05). • PPI was stopped in 61% at 1 y.

Inoue et al. GIE 2017

GERD Q score 0-12

ARMS• Conclusion: • Results strongly suggest the short-term effectiveness of

ARMS for refractory GERD. • Long-term follow-up data will be awaited.

COMPARISON OF TIF AND STRETTASYSTEMATIC REVIEW AND METAANALYSIS

• No RCT to compare these 2 techniques.

• Limitations of this article:• The total sample size of 397 is small

(Stretta n=101, TIF n=296)

• Author conclude that both Stretta and TIF can fill the therapy gap between PPI medication and laparoscopic fundoplication.

• Both methods are relatively safe, however, TIF could be superior to Stretta

Obuobi et al. Int Surg J. 2018

COMPARISION OF DIFFERENT ENDOSCOPIC TECHNIQUES


TAKE HOME MESSAGES-PPIs remain the cornerstone of medical management of GERD

-Endoscopic treatment is not meant to replace PPIs

-They may bridge the unmet gap between PPIs and surgery

-More studies with long-term follow-up and randomized comparisons are required to establish the role of endoscopic treatment in the management of GERD.

-Studies assessing the predictive factors for response or non-response will help in minimizing failures and maximizing efficacy.

Documents

Endoscopic treatment of GERD - LSGE€¦ · TREATMENT OPTIONS FOR GERD Sandhu et al. Gut Liver 2018; 12(1):7-16. GERD MANAGEMENT ALGORITHM Persisting symptoms Suspected GERD. PPI