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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
Gastrointestinal Endoscopy 2017 86, 931-948DOI: (10.1016/j.gie.2017.08.001)
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
Gastrointestinal Endoscopy 2017 86, 931-948DOI: (10.1016/j.gie.2017.08.001)
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
Gastrointestinal Endoscopy 2017 86, 931-948DOI: (10.1016/j.gie.2017.08.001)
ENDOSCOPIC ANTI-REFLUX DEVICES
Stretta catheter (Mederi Therapeutics, Greenwich, Connecticut).
Thosani et al. GIE 2017;86(6),931-948
Figure 7
Gastrointestinal Endoscopy 2017 86, 931-948DOI: (10.1016/j.gie.2017.08.001)
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.
Gerson et al. Chirurgia 2018
METAANALYSIS OF THE 3 RCT’S
Gerson et al. Chirurgia 2018
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
Nabi et al. Clin Endosc 2016
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)
Corley et al. Gastroenterology 2003
STRETTA – DECREASE IN PPI USE AT 6 MONTHS
Corley et al. Gastroenterology 2003
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.
Lipka et al. Clinical Gastroenterol Hepatol 2015
METAANALYSIS OF THE AVAILABLE RCT’S – LIPKA ET AL.
Lipka et al. Clinical Gastroenterol Hepatol 2015
METAANALYSIS OF RCT’S AND COHORT STUDIES- HRQL
Fass et al. Surg Endosc 2017
METAANALYSIS OF RCT’S AND COHORT STUDIES – HEARTBURN SYMPTOM SCORE
Fass et al. Surg Endosc 2017
METAANALYSIS OF RCT’S AND COHORT STUDIES – RELIANCE ON PPI
Fass et al. Surg Endosc 2017
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.
Fass et al. Surg Endosc 2017
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
Nabi et al. Clin Endosc 2016
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.