GERD: Pitfalls and Pearls

Transcription

1 GERD: Pitfalls and Pearls Gary W. Falk, M.D., M.S. Professor of Medicine Division of Gastroenterology Perelman School of Medicine of the University of Pennsylvania Conflicts of Interest Nothing to disclose 1

2 Learning Objectives How do I approach patients with classic GERD symptoms? What should I tell patients about risks of PPI therapy? How should I approach patients with PPI refractory symptoms? How should I deal with extraesophageal GERD symptoms? What about other options for GERD therapy? Learning Objectives How do I approach patients with classic GERD symptoms? What should I tell patients about risks of PPI therapy? How should I approach patients with PPI refractory symptoms? How should I deal with extraesophageal GERD symptoms? What about other options for GERD therapy? 2

3 GERD: Montreal Definition A condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications > 2 heartburn episodes/week Adversely affect an individual s well being From Vakil N et al. Am J Gastroenterol 2006;101: The Montreal Classification: GERD Symptom Definitions Heartburn & regurgitation are the characteristic symptoms of typical reflux syndrome Heartburn Burning sensation in retrosternal area Regurgitation Perception of flow of refluxed gastric contents into mouth or hypopharynx From Vakil N et al. Am J Gastroenterol 2006;101:

4 GERD Diagnostic Approach: ACG Guidelines If history typical for uncomplicated heartburn, initial trial of empiric PPI therapy reasonable Typical symptoms responding to therapy require no diagnostic testing From Katz PO et al. Am J Gastroenterol 2013;108: PPIs for GERD In equivalent doses different PPI preparations do not show statistically significant difference in healing effect Double dose therapy associated with modest improvement in healing of erosive esophagitis NNT-25 From Moayyedi P et al. Cochrane Database of Systematic Reviews 2007;2 4

5 Lifestyle Intervention in GERD: Systematic Review Weight loss Decreased acid exposure Decreased GERD symptoms (dose dependent) Tobacco cessation Decreased symptoms in normal weight individuals From Ness-Jensen E et al. Clin Gastroenterol Hepatol 2016;14: Lifestyle Intervention in GERD: Systematic Review Dietary intervention Decreased supine acid exposure with early meals Head of bed elevation with wedge Decreased acid exposure From Ness-Jensen E et al. Clin Gastroenterol Hepatol 2016;14:

6 Potential Candidates for Barrett s Esophagus Screening: 2016 ACG Guidelines Males Chronic or frequent GERD + > 2 risks: Age > 50 yrs. Caucasian Central obesity Current or past smoking First degree relative From Shaheen NJ et al. Am J Gastroenterol 2016;111: Learning Objectives How do I approach patients with classic GERD symptoms? What should I tell patients about risks of PPI therapy? How should I approach patients with PPI refractory symptoms? How should I deal with extraesophageal GERD symptoms? What about other options for GERD therapy? 6

7 PPI Safety Concerns Metabolic bone disease/hip fracture Infection C. difficile Bacterial gastroenteritis Pneumonia Clopidogrel Chronic kidney disease Interstitial nephritis B 12 deficiency Hypomagnesemia Microscopic colitis MI Dementia Acid rebound SIBO Reported Associations With PPI Use & Adverse Events From Kia L et al. Nat Rev Gastroenterol Hepatol 2016:13:

8 Zones of Potential Bias in Observational Studies Causal inference should be guarded in if OR in zone of bias From Vaezi MF et al Gastroenterology 2017;153: PPI Safety Concerns in Perspective Data on PPI risks from observational studies Strength of association Modest Statistically significant Observational studies subject to bias & other methodological weakness Criteria for causation generally not met From Freedberg DE et al. Gastroenterology 2017;152:

9 Antireflux Surgery: Side Effects & Complications From Richter JE. Clin Gastroenterol Hepatol 2013;11: AGA Best Practice Advice For Use Of PPIs GERD & acid related complications [erosive esophagitis, peptic stricture]: Take PPIs for short term healing, maintenance of healing & long term symptom control In uncomplicated GERD responsive to short term PPI: Attempt to stop or reduce therapy If unsuccessful consider ph monitoring prior to lifelong therapy to distinguish GERD from functional syndrome From Freedberg DE et al. Gastroenterology 2017;152:

10 AGA Best Practice Advice For Use Of PPIs If Barrett s and symptomatic GERD Take long term PPI If Barrett s and asymptomatic GERD Consider long term PPI Dose of long term PPIs should periodically be revisited to use lowest dose to control symptoms From Freedberg DE et al. Gastroenterology 2017;152: AGA Best Practice Advice For Use Of PPIs No role for probiotics No role for routinely altering intake of Ca, B-12 or Mg No need to screen or monitor Bone mineral density Creatinine Mg Vitamin B12 From Freedberg DE et al. Gastroenterology 2017;152:

11 PPI Checklist Question What is indication? How frequent are symptoms? Assess Has cessation been tried? Has dose reduction been tried? Have lifestyle measures been maximized? Learning Objectives How do I approach patients with classic GERD symptoms? What should I tell patients about risks of PPI therapy? How should I approach patients with PPI refractory symptoms? How should I deal with extraesophageal GERD symptoms? What about other options for GERD therapy? 11

12 Refractory GERD: No Agreement on Definition Lack of response to once daily PPI Lack of response to twice daily PPI 2012 definition: Persistent symptoms of heartburn or regurgitation not responding to twice daily PPI for 12 weeks Seen in up to 40% of patients From Sifrim D et al. Gut 2012;61: PPI Refractory Reflux Symptoms: Differential Diagnosis GERD Hypersensitvity Functional heartburn Functional chest pain Achalasia Distal esophageal spasm EoE From Kahrilas PJ et al. Neurogastroenterol Motil 2015;27:

13 PPI Efficacy in GERD From Boeckxstaens G et al. Gut 2014;63: PPI Refractory Reflux Symptoms: Approach Optimize PPI therapy Before meal dosing BID Observe sensible lifestyle measures Diagnostic testing EGD + biopsies Manometry ph off therapy preferable From Kahrilas PJ et al. Neurogastroenterol Motil 2015;27:

14 ph Monitoring Performance Characteristics Erosive esophagitis Sensitivity: % Specificity: % NERD Sensitivity: < 71% From Katz PO et al. Am J Gastroenterol 2013;108: Symptom Association in ph Monitoring Symptom index [> 50%] Sensitivity 80% Specificity 35% Symptom association probability [> 95%] Sensitivity 73% Specificity 65% Neither validated Information needs to be interpreted in conjunction with other testing & clinical setting From Vaezi MF. Gastroenterology & Hepatology 2012;8:

15 ph Testing Off Therapy When diagnosis of GERD not yet established BRAVO ph preferred Documents abnormal acid exposure Establish relationship between symptoms & reflux events Classify patients as: NERD Hypersensitive esophagus Functional heartburn From Sifrim D et al. Gut 2012;61: ph Testing On Therapy Diagnosis of GERD established but symptoms persist Done on bid PPI Impedance ph preferred Low yield of BRAVO ph on therapy Establish relationship between symptoms and reflux events [acid + nonacid] Excludes GERD as cause of persistent symptoms Virtually no outcome data! From Sifrim D et al. Gut 2012;61:

16 Approach to Patients With Normal EGD + Biopsies From Aziz Q et al. Gastroenterology 2016;150: Reflux Hypersensitivity: Rome IV Heartburn and/or chest pain Normal EGD + biopsies Absence of major esophageal motor disorder Triggering of symptoms by reflux events despite normal acid exposure From Aziz Q et al. Gastroenterology 2016;150:

17 Reflux Hypersensitivity: Treatment Standard or double dose PPI Very little evidence of positive response to surgery Pain modulators TCA SSRI Serotonin/noradrenergic reuptake inhibitors Gabapentenoids From Aziz Q et al. Gastroenterology 2016;150: Functional Heartburn: Rome IV Retrosternal burning discomfort or pain refractory to optimal antisecretory therapy Absence of: GERD Symptom-reflux correlation Histopathologic mucosal abnormalities Major motor disorders Structural explanations From Aziz Q et al. Gastroenterology 2016;150:

18 Psychologic Features of Functional Heartburn Increased: Anxiety Somatization Poor social support From Aziz Q et al. Gastroenterology 2016;150: Pain Modulators for the Treatment of Functional Esophageal Disorders From Aziz Q et al. Gastroenterology 2016;150:

19 Learning Objectives How do I approach patients with classic GERD symptoms? What should I tell patients about risks of PPI therapy? How should I approach patients with PPI refractory symptoms? How should I deal with extraesophageal GERD symptoms? What about other options for GERD therapy? Montreal GERD Consensus Conference: Atypical Symptoms GERD & extraesophageal symptoms are associated Extraesophageal symptoms rarely occur in the absence of typical GERD symptoms Extraesophageal symptoms typically multifactorial Data substantiating beneficial effect of treatment weak From Vakil N et al. Am J Gastroenterol 2006;101:

20 Extraesophageal Manifestations of GERD: ACG Practice Guideline Evaluation of non-gerd causes should be considered in all patients with atypical presentations A diagnosis of reflux laryngitis cannot be made by the ENT examination Poor interobserver agreement Abnormalities seen in 80% of healthy controls A PPI trial is recommended in patients with typical symptoms Reflux monitoring should be considered in patients without classic GERD symptoms prior to PPI trial Surgery should not be performed to treat atypical symptoms if not responding to PPI From Katz PO et al. Am J Gastroenterol 2013;108: Alternative Laryngeal Findings With Symptoms Overlapping Suspected LPR Muscle tension dysphonia Vocal cord paralysis Presbylaryngitis Irritable larynx syndrome Cancer Recurrent respiratory papillomatosis Laryngotracheal stenosis Phonotraumatic lesion Vocal cord hemorrhage Polypoid corditis Vocal cord scarring Vocal cord granuloma Laryngeal Candidiasis Zenker s diverticulum Paradoxical vocal cord motion From Francis DO et al. Clin Gastroenterol Hepatol 2015;13:

21 Chronic Cough & GERD: CHEST Guidelines Common causes of cough should be considered first Environmental/ occupational irritants Smoking ACE inhibitors Asthma Rhinosinus conditions Abnormal chest X-ray findings Nonasthmatic eosinophilic bronchitis Suppurative lung disease From Kahrilas PJ et al. Chest 2016;150: Chronic Cough & GERD: CHEST Guidelines No evidence that GERD therapy can improve or eliminate cough PPIs demonstrate no benefit in isolation From Kahrilas PJ et al. Chest 2016;150:

22 Chronic Cough & GERD: CHEST Guidelines In patients with cough suspected to be due to reflux-cough syndrome: Weight loss if obese Elevate head of bed Avoid late meals PPIs only if heartburn or regurgitation reported From Kahrilas PJ et al. Chest 2016;150: Chronic Cough & GERD: CHEST Guidelines In patients with suspected cough thought due to reflux without hearburn or acid regurgitation No PPI should be used Standard antireflux surgery indications and evaluation From Kahrilas PJ et al. Chest 2016;150:

23 Learning Objectives How do I approach patients with classic GERD symptoms? What should I tell patients about risks of PPI therapy? How should I approach patients with PPI refractory symptoms? How should I deal with extraesophageal GERD symptoms? What about other options for GERD therapy? RCT of Laparoscopic Antireflux Surgery Vs. Esomeprazole for GERD 92% 85% From Galmiche J. et al. JAMA 2011;305:

24 Laparoscopic Fundoplication Vs. Medical Management of GERD Considerable uncertainty regarding balance of benefits & harms of fundoplication vs. long term PPI treatment From Garg SK et al. Cochrane Databases of Systematic Reviews 2015;11:CD Laparoscopic Fundoplication for GERD: Systematic Review Pros Symptomatic & physiologic relief out to 10 years Reduces acid exposure Improves QOL Decreases erosive esophagitis Cons Short term AE Dysphagia Gas bloat Inability to vomit At 10 years: Recurrent heartburn in 35% Recurrent regurgitation in 30% PPI use in 18% Redo surgery in 10% From Hillman L et al. Dis Esoph 2017;30:

25 Magnetic Sphincter Device From Ganz R et al. Clin Gastroenterol Hepatol 2016;14: Magnetic Sphincter Device For GERD N=100 > 6 mos of GERD Partial response to PPI therapy Abnormal acid exposure by ph monitoring Exclusions Large hiatal hernia LA C/D esophagitis BMI > 35 Barrett s esophagus Motility abnormalities Dysphagia > 3 X/week From Ganz R et al. New Engl J Med 2013;368:

26 Magnetic Sphincter Device For GERD Primary end points Normalization of acid exposure (< 4.5%): 58% Reduction of > 50% acid exposure: 67% Adverse events: Device removal-4% Dysphagia Early 68% 1 year 11% Crural repair in 34% From Ganz R et al. New Engl J Med 2013;368: Reflux Control Before & 5 Years After Placement of Magnetic Sphincter Device Healing of esophagitis in 26/34 (76.5%) assessed From Ganz RA et al. Clin Gastroenterol Hepatol 2016;14:

27 Esophageal Sphincter Device For GERD: Safety of First 1000 Patients Outcome % Intra/perioperative complications 0.1% Readmission 1.3% Dilation 5.6% Device removal 3.4% Device erosion into lumen 0.1% From Lipham JC. Dis Esoph 2015;28: Magnetic Sphincter for GERD: Systematic Review Pros Less extensive surgery Standardized technique Symptomatic & physiologic relief Reduces acid exposure Improves QOL Decreases PPI use Cons Short term AE Dysphagia Less versatile Large hernias Severe erosive GERD Lack of head to head comparisons Short term results only From Hillman L et al. Dis Esoph 2017;30:

28 Transoral Fundoplication From Hunter JG et al. Gastroenterology 2015;148: Transoral Fundoplication Vs Omeprazole For Regurgitation RCT sham controlled trial [N=129] Troublesome regurgitation despite omeprazole 40 mg daily Mild symptoms > 2 days/week Moderate/severe symptoms > 1 day/week Hiatal hernia < 2 cm Primary end 6 mos Elimination of troublesome regurgitation TF-67% Sham-45% [QD or BID omeprazole] From Hunter JG et al. Gastroenterology 2015;148:

29 Electrical Stimulation Therapy of the LES Acid Exposure After LES Stimulator No Change in LES pressure noted From Kappelle WFW et al. Aliment Pharmacol Ther 2015;42:

30 Summary For uncomplicated GERD the goal of therapy remains lowest dose of medication to control symptoms Do not forget simple lifestyle measures! PPI AE controversy driven by large data base association studies with low magnitude of effect & methodologic flaws Summary ph testing off therapy most useful approach for GERD patients not responding to PPI Relationship of GERD to extraesophageal symptoms becoming more tenuous Eventual role of alternatives to standard medical & surgical therapy remains to be determined 30

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