GERD and its Management. BY DR.ANIL S.O

GERD

1. GERD and its Management Dr Anil S P MBBS, MS, FMAS, FSGE Consultant - Surgical Gastroenterology People Tree Hospitals

2. Heidelbaugh JJ et. al UMHS GERD Guideline. 2013 GERD may manifest atypically as Pulmonary (asthma, chronic cough), Laryngeal (laryngitis, hoarseness, sore throat, globus , throat clearing), or Cardiac (chest pain) symptoms, Often without symptoms of heartburn & regurgitation Mechanisms Direct contact and micro-aspiration of small amounts of noxious gastric contents Triggering local irritation, and cough, and Acid stimulation of vagal afferent neurons in the distal esophagus causing non-cardiac chest pain and vagally-mediated bronchospasm or asthma Laryngeal neuropathy has been implicated as a cause for laryngitis symptoms and cough.

3. Heidelbaugh JJ et. al UMHS GERD Guideline. 2013 Treatment Aggressive acid reduction using PPIs twice daily before meals for at least 2-3 months : Considered the standard treatment for atypical GERD Responsive to acid suppressive therapy : PPIs adjusted to the minimal necessary dose for symptom control & optimally treating other etiologies requiring treatment. Unresponsive patients : PPI doses increased/ change of PPI considered. Double blind, placebo controlled trials not shown significant benefit for PPI BD treatment for laryngeal symptoms. Similar trials in asthma: Marginal benefits in FEV1 rates only when nocturnal GERD symptoms are also present. Anti-reflux surgery: controlling asthma through prevention of GERD has lower rate of success vs. anti-reflux surgery aimed at treating heartburn (45-50% vs. 80-90% respectively)

4. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Treatment (ACG Guideline) Careful evaluation for non-GERD causes . Reflux laryngitis diagnosis should not be made based solely upon laryngoscopy findings. PPI trial: recommended to treat extraesophageal symptoms in patients who also have typical symptoms of GERD. Reflux monitoring: considered before PPI trial in patients with extraesophageal symptoms who do not have typical symptoms of GERD Upper endoscopy is not recommended as a means to establish a diagnosis of GERD-related asthma, chronic cough, or laryngitis Non-responders to a PPI trial should be considered for further diagnostic testing Surgery should generally not be performed to treat extraesophageal symptoms of GERD in patients who do not respond to acid suppression with a PPI .

5. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Heidelbaugh JJ et. al UMHS GERD Guideline. 2013 Efficacy of lifestyle interventions for GERD

6. Heidelbaugh JJ et. al UMHS GERD Guideline. 2013

7. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Complications associated with GERD Erosive esophagitis: Los Angeles (LA) classification to be used when describing the endoscopic appearance of erosive esophagitis. LA Grade A esophagitis: undergo further testing to confirm the presence of GERD. Barrett’s esophagus: Repeat endoscopy in patients with severe erosive reflux disease after a course of antisecretory therapy to exclude underlying Barrett’s esophagus. Symptomatic Barrett’s esophagus can be treated in a similar fashion to patients with GERD without Barrett’s esophagus. Undergo periodic surveillance according to guidelines

8. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Peptic stricture: Continuous PPI therapy recommended following peptic stricture dilation to improve dysphagia and reduce the need for repeated dilations. Complex strictures: Injection of intralesional corticosteroids can be used in refractory, complex strictures due to GERD Schatzki rings: PPI treatment suggested post dilation in patients with lower esophageal (Schatzki) rings Complications associated with GERD

9. REFRACTORY GERD Triadafilopoulos G. World J Gastroenterol. 2014 Jun 28; 20(24): 7730–7738.

10. REFRACTORY GERD Treatment-refractory GERD is a condition in which symptoms or mucosal lesions caused by reflux of gastric contents are not responding to a high dose of PPI The term refractory GERD encompasses a heterogeneous group of patients that may differ in Symptom frequency and severity PPI dosing regimen (once or twice daily) Response to therapy (from partial to absent)

11. REFRACTORY GERD Refractory GERD has a significant impact on QOL Persistent reflux symptoms on PPI therapy are associated with reduced physical and mental health-related QOL The most important goal of the diagnostic evaluation in these patients is to differentiate those with persistent reflux, from those with non-GERD etiologies

12. REFRACTORY GERD Algorithm for the evaluation of refractory GERD Am J Gastroenterol 2013; 108:308 – 328

13. REFRACTORY GERD ACG Guideline’s recommendations The first step in management of refractory GERD is optimization of PPI therapy Upper endoscopy should be performed in refractory patients with typical or dyspeptic symptoms principally to exclude non-GERD etiologies In patients in whom extraesophageal symptoms of GERD persist despite PPI optimization, assessment for other etiologies should be pursued Concomitant evaluation by ENT, pulmonary, and allergy specialists . Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328;

14. REFRACTORY GERD ACG Guideline’s recommendations Patients with refractory GERD and showing normal endoscopy & no extra esophageal symptoms, should undergo ambulatory reflux monitoring Reflux monitoring off medication can be performed by any available modality (pH or impedance-pH) Testing on medication should be performed with impedance-pH monitoring in order to enable measurement of nonacid reflux Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328;

15. REFRACTORY GERD ACG Guideline’s recommendations Refractory patients with objective evidence of ongoing reflux as the cause of symptoms should be considered for additional antireflux therapies that may include surgery Patients with negative testing are unlikely to have GERD and PPI therapy should be discontinued Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328;

16. PPIs: POLYMORPHISM IN METABOLISM The elimination of all PPI involves hepatic oxidation mediated primarily by CYP2C19 isoform Genetic polymorphism in CYP2C19 genotypes leads to 3 categories of PPI metabolism Extensive or Rapid metabolizers Intermediate metabolizers Poor or Slow metabolizers

17. PPIs: POLYMORPHISM IN METABOLISM Slow metabolizers show greater antisecretory effect of PPIs than rapid and intermediate metabolizers Because of these slow metabolizers are much more prone to drug interactions related to PPIs While rapid metabolizers may develop resistance to PPIs

18. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Medical options for GERD patients with incomplete response to PPI therapy ( Limited ) Addition of bedtime H 2 RA : recommended for patients with symptoms refractory to PPI Multiple intragastric pH studies demonstrated overnight pH control H 2 RA might be most beneficial if dosed on as needed basis in patients with provocable night-time symptoms and patients with overnight esophageal acid reflux Prokinetic therapy (metoclopramide) in addition to PPI: Increase LESP, enhance esophageal peristalsis and augment gastric emptying Clinical data showing additional benefit of metoclopramide to PPI therapy has not been adequately studied In the absence of gastroparesis, there is no clear role for metoclopramide in GERD.

19. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Medical options for GERD patients with incomplete response to PPI therapy ( Limited ) Domperidone : Peripherally acting dopamine agonist ; Efficacy equivalent to that of metoclopramide for gastric emptying Little to no data are available in GERD Monitoring for QT prolongation: small risk for ventricular arrhythmia and sudden cardiac death Baclofen: GABA(b) agonist Reduce transient LES relaxations, reflux episodes, postprandial acid & non-acid reflux events, nocturnal reflux activity & belching episodes Two short-term RCTs that demonstrated symptomatic improvement with this agent Usage limited by side effects - dizziness, somnolence, and constipation.

20. Surgical Treatment Indications Esophagitis Stricture Barrett’s metaplasia Medication failure Purpose of surgery  restoration the LES Reasons to refer GERD patients for surgery Desire to discontinue medical therapy, non-compliance, side-effects with medical therapy, the presence of a large hiatal hernia, esophagitis refractory to medical therapy, or persistent symptoms documented to be caused by refractory GERD. Refractory dyspeptic symptoms (nausea, vomiting, & epigastric pain) less likely to demonstrate symptomatic response . Highest surgical responses: Typical symptoms of heartburn and / or regurgitation that demonstrate good response to PPI therapy or have abnormal ambulatory pH studies with good symptom correlation

21. Katz P.O. et. al. Am J Gastroenterol 2013; 108:308 – 328; Surgical Options For GERD (ACG Guideline) Surgical therapy - a treatment option for long-term therapy. Generally not recommended in patients who do not respond to PPI therapy. Preoperative ambulatory pH monitoring mandatory in patients without evidence of erosive esophagitis. All patients should undergo preoperative manometry to rule out achalasia or scleroderma-like esophagus. Obese patients should be considered for bariatric surgery. Gastric bypass would be the preferred operation. Usage of current endoscopic therapy or transoral incisionless fundoplication cannot be recommended as an alternative to medical or traditional surgical therapy.

22. Surgical Treatment Most studies indicate that the majority of patients are symptom-free (70-95%) Recent studies suggest that after 5 years, up to 1/3 of patients required PPI to control symptoms. At 10 years, up to 50% require PPIs Side-effects: gas-bloat symptoms, diarrhea, dysphagia

23. Endoscopic Treatments In development with ongoing studies Most try to improve LES function in some manner Not quite ready for prime time in community practice

24. Stretta procedure An upper gastrointestinal endoscopy with delivery of thermal energy to the muscle of the lower esophageal sphincter and gastric cardia for the treatment of GERD The Society of American Gastrointestinal and Endoscopic Surgeons has concluded that Stretta is an appropriate therapy for patients with GERD who are18 years of age or older with symptoms of heartburn and/or regurgitation for 6 mnths or more, who have been completely or partially responsive to anti-secretory pharmacologic therapy, and who have declined laparoscopic fundoplication Triadafilopoulos G. World J Gastroenterol. 2014 Jun 28; 20(24): 7730–7738.

25. Stretta procedure Decrease in symptom score Decreased PPI No effect on LESP No effect on acid exposure Some serious thermal injury complications

26. Endoscopic suturing

27. Endoscopic suturing Decreased heartburn symptoms PPI eliminated in 74% of patients at 6 months Decreased esophageal acid exposure; however, only 30% completely normalized Long term follow-up needed

28. GERD UNMET NEEDS

29. GERD: UNMET NEEDS Despite the major progress made in management of GERD, it should be realized that there are still many unmet needs that are not addressed by PPIs and LARS (Laparoscopic anti-reflux surgery) Approximately 20–30% of reflux patients, especially those with non acid reflux or extraoesophageal manifestations, are clearly poor responders to PPI therapy Unfortunately for this group of patients, LARS is also less likely to achieve satisfactory results than in PPI responders

30. GERD: UNMET NEEDS PPI resistance is one of the reason for failure of treatment GERD One of the main reason for development of resistance to PPIs is the genetic polymorphism associated with metabolism of PPIs

31. GERD: UNMET NEEDS Mechanisms potentially responsible for PPI resistance United European Gastroenterol J. 2013 Jun;1(3):140-50.

32. Thank You!!!