GERD Panel

Mojgan Forootan
Hossein Nobakht MD
Armideh Mashayekh MD

Iradj Maleki MD
Mazandaran University of Medical Sciences
Gut & Liver Research Center
1
 Learning objectives

 Definition
 Pathophysiology
 Epidemiology
 Problems in the diagnosis
 Problems in the management
 New approaches in the management
 Diagnosis of GERD

 GERD is a condition that develops  Symptom-based diagnosis

when the reflux of stomach contents
causes troublesome
symptoms and/or complications  Overlap with other organic and
functional diseases
 GERD is classified based on the  Functional heartburn
appearance of the esophageal mucosa
on upper endoscopy into the following:  Esophageal hypersensitivity
 Erosive esophagitis  Rumination syndrome
 Non-erosive reflux disease  Eosinophilic esophagitis

3
 Pathophysiology
of GERD

4
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
Epidemiology of GERD

5
Trend in GERD prevalence worldwide

6
Epidemiology of GERD in Iran
 Epidemiology of GERD in Iran
Reflux prevalence Response Sample Place of study Date of study
rate size
yearly monthly weekly daily
>85% 18.4% 6.8% 1.9% 84.5% 1700 Tehran 2004-2005
33% 89% 748 Fars Province 2006
15.4% 54.9% 1978 Shiraz 2004
28.7% 18.2% 94.% 2500 Tehran
21.2% 84.8% 2500 Tehran 2005
39.7% 20.9% 7.9% 10.9% 700 Tehran 1999

9.1% 90.6% 6325 Firoozkoh 2006

13% 6.3% 95% 620 Tabriz 2005
2.7% 4207 Tabriz 2000
29.2% 782 Firoozkoh 2006
34.1% 26.8% 95% 522 Tabriz 2005
21.5% 12.9% 12.1% 97.9% 2400 Isfahan 2004
25.5% 86.71% 5429 Shahrekurd
12.3% 98.4% 1016 Gonbadkavoos 2005
 Epidemiology of GERD in Iran
35 34.1
33

30 29.2 28.7

26.8
25.5
25

21.5 21.2
20.9

20 18.4 18.2
Monthly
15.4
Weekly
15
12.9 13 Daily
12.1 12.3
10.9

10 9.1
7.9
6.8 6.3

5
2.7
1.9

0
1999 2000 2004 2004 2004 2004 2005 2005 2005 2005 2006 2006 2006 2008
GERD Prevalence studies from Iran
Patients with endoscopic esophagitis gaining relief of heartburn after
starting on a proton pump inhibitor

10
Summary of proton pump inhibitor (PPI) efficacy for various
GERD syndromes as assessed in randomized controlled trials

11
 Evaluation of refractory GERD symptoms
A study of 106 patients

Abnormal acid exposure (AET>6%)

Normal acid exposure (AET<4%)

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
GERD NERD Reflux hypersensitivityH Functional Heartburn EOE Achalasia Motility

12
TVK Herregods, Neurogastroenterol Motil (2015)
Where are we in the field of diagnosis and management
of GERD/ NERD/ refractory symptoms?

13
Case 1

14
 Case 1

 32 years male
 Heartburn and intermittent regurgitation for 8-9 months
 Occasional retrosternal pain with special food intake
 No dysphagia or odynophagia, no epigastric pain
 No significant medical history
 Smoker since 4-5 years (half a pack/ day)

15
 Case 1

 What is your recommendation?

 Offer treatment?
 Need further data from history and physical exam?
 Perform EGD?
 Refer to cardiologist?

16
Recommendations

17
 Case 1

 The patient was treated with lansoprazole 30 mg daily

 After 4 weeks he has partial response, has just occasional heartburn
 what to do next?

 Continue treatment?
 Need further data from history and physical exam?
 Perform EGD?
 Perform pH monitoring (pH-metry)?
 Recommend other medical treatment measures?

18
 Case 1

 The patient does not come for a visit until 9 months later
 He had been good with PRN Ranitidine
 For the last 2 months the symptoms have increased dramatically
 Occasional dysphagia is present
 The patient is concerned of his disease and seems anxious

19
 Case 1

 Lifestyle modification for GERD patients:

 Smoking
 Ethanol use
 Food elimination
 Head of bed elevation
 Avoid sleeping after meals

 Are these recommendations evidence based?

20
 Case 1

 The patient asks for diagnostic evaluation

 Do you agree with diagnostic evaluation in this setting?

 If yes, which modality do you recommend?

 EGD
 Barium swallow
 Reflux monitoring (pH metry)
 Manometry
21
 Case 1

 What if you see this in the

endoscopy?

22
 Case 1

 What if you see this in the

endoscopy?

23
 Case 1

 Does it differ for your management  Maintenance PPI treatment

if you see this at endoscopy:
 Equivocal GERD
 LA class A-B versus C-D esophagitis?  unequivocal GERD

 Repeat EGD?!

24
 Case 1

 Does it differ for your management

if you see this at endoscopy:

 Bile stained secretions in stomach?

25
 Case 1

 What if you see this in the

endoscopy (site upper esophagus
just after the UES)?

26
A patient with globus & sore throat
A 7 months course

27
 Case 1

 The patient had used lansoprazole daily and even BID with partial
responses. He has nearly 2-3 times a week heartburn
 Considering that the patient has endoscopic reflux at EGD, what is your
next medical step?
 Lansoprazole TDS?
 Change the PPI?
 Add domperidone or baclofen?
 Add bedtime Famotidine?

28
 Case 1

 The patient was using pantoprazole 40 mg BID

 He is a busy man, but used the pills before breakfast and supper
 He is not satisfied with the result completely
 What reason could be the reason?

1. Proper timing of the traditional PPIs (30-60 min before meals)

2. New PPIs (dexlansoprazole)
3. Potassium-competitive acid blockers (P-CABs)

29
 Case 1

 What if you see this in the

endoscopy (site lower esophagus/ Z
line) after a 2-3 months course of
high dose PPI therapy?

30
Prague classification for columnar metaplasia

31
Prague classification
for columnar metaplasia

32
 Sites to inspect during endoscopy

Upper esophagus Around LES

 Inlet patch  Z line

 Light versus NBI  Mucosal breaks
 Significance of inlet patch  Ulcers
 Polyps

 Hiatal hernia (from upside & downside)

33
 Quality standards in upper
gastrointestinal endoscopy

Quality standards in upper gastrointestinal endoscopy: a position statement

of the British Society of Gastroenterology …, Gut. 2017 Nov;66(11):1886-1899 34
Use of NBI in better visualization of distal esophagus

35
36
An approach to (Refractory) GERD

37
 PPI use cost in Iran

 At least 2 studies have evaluated

the cost of GERD in Iranian
population
 First study:
 Direct yearly cost: PPP$97.70
 Indirect yearly cost: PPP$13.7
 Second study:
 Yearly cost per patient: PPP$195

38
 Financial Burden of PPI use
 Omeprazole: 250 – 500 Tooman/ cap
 Pantoprazole: 400 – 2400 Tooman/ Tab
 Lansoprazole: 600 Tooman/ Cap
 Esomeprazole: 400 – 2300 Tooman/ Cap

 A patient using Omep. daily for 1 year  300 T x 30 x 12 = 108,000 T

 A patient using Panto. daily for 1 year  1000 T x 30 x 12 = 360,000 T
 A patient using Lanzo. daily for 1 year  600 T x 30 x 12 = 216,000 T
 A patient using Eso. daily for 1 year  1500 T x 30 x 12 = 540,000 T
 PPI cost estimation

 Mean prevalence of GERD in Iran(estimation): 10%

 Mean prevalence of regular PPI use(estimation): 5%
 Iran’s population: 80,000,000

 Omep. yearly usage cost: 108,000 x 5% x 80,000,000 = 432,000,000,000 T

 Panto. yearly usage cost: 360,000 x 5% x 80,000,000 = 1,440,000,000,000 T

 Consider also the GP/GI/ cardiologist visits plus EGD/ cardiac workups
910,989,335,800 Rials
Deprescription of PPIs!

42
Burning sensation

43
44
 Case 2

 A 42 years old lady complaining of retrosternal discomfort > one year

 She has intermittent heartburn, globus and occasional regurgitation sensation
 The symptoms are severe enough to awaken her at nights
 She had been visited by many physicians including GPs, internists and now
comes to you
 She has used famotidine, omeprazole and lansoprazole with partial responses
 Last month she had used pantoprazole 40 BID with no complete response
 No diagnostic evaluation has been done yet
 What is your next step?

45
Case 2

46
 Interpretation of “Normal EGD”

 Is normal endoscopy against the diagnosis of GERD?

 Yes?
 No ?

 Is normal endoscopy enough for definite diagnosis of GERD?

 Yes ?
 No?

47
Diagnostic value of EGD in the setting of GERD

 How can EGD definitely diagnose GERD?

 LA class C or D
 Barrett’s esophagus (Biopsy proven)
 Peptic stricture

48
 Interpretation of “PPI Response”

 Is positive PPI response enough for the diagnosis of GERD?

 Yes?
 No?

 Is negative PPI response enough for ruling out GERD?

 Yes?
 No?

49
 Case 2

 Is endoscopic biopsy needed

in the setting of GERD
patients?
 When?
 Why?
 How?

50
 Case 2

 What is your next step?

 Perform pH monitoring?
 Perform manometry?
 Add bedtime H2 blocker?
 Add baclofen?
 Add tricyclic?

51
 Case 2

 In this setting of “not complete to 8 weeks of double dose of PPI” and

“normal EGD” what is the next step?

 Reflux monitoring/ pH metry

 Acid Exposure Time (AET)
 > 6% (definite reflux disease)
 4-6% (grey zone, further evaluation is needed)
 <4% (definitely no reflux disease)

52
 pH monitoring

 On therapy or off therapy?

 What is meant with off therapy? How long to stop PPI before testing?

53
Case 2

54
55
 pH monitoring or pH impedance?

 Catheter based pH monitoring or

capsule pH monitoring?

56
 Role of reflux monitoring

 Symptom index (SI)

 The percentage of symptom events preceded by reflux episodes,66 and
the optimal SI threshold for heartburn is 50%

 Symptom association probability (SAP)

 It takes into account 2 min periods with and without reflux episodes and
symptom events, and applies a statistical test. A SAP >95% corresponds
to a <5% chance that symptoms and reflux episodes could have
co-occurred just by chance
57
Novel metrics in the diagnosis of uncertain cases

 Count of reflux episodes (> 80/day & <40/day versus 40-80/day)

 Impedance

58
 Role of esophageal manometry

 Helpful in the grey zone of pH monitoring

 Not useful as a stand alone option for diagnosis of GERD
 Mandatory for catheter based pH monitoring (finding LES)
 Mandatory before anti-reflux surgery (R/O achalasia)
 Helpful in the diagnosis of rumination syndrome

59
 Refractory regurgitation

 Beware of rumination syndrome

60
Advanced, non-medical treatment options

61
 Lyon Consensus

62
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
 Lyon Consensus

63
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
 Lyon Consensus

64
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
 Lyon Consensus

65
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
 66
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
 67
Gyawali CP, et al. Gut 2018 (Lyon Consensus)
Gyawali CP, et al. Gut 2018 68
(Lyon Consensus)
Refractory heartburn (HB) assessment

Proven GERD  Unproven GERD 

pH impedance on PPI pH monitoring or pH impedance off therapy

AET > 6% AET < 4% AET > 6% AET <4%

SAP positive SAP positive
True refractory
Esophageal NERD Esophageal
GERD
hypersensitivity hypersensitivity

Escalate SAP negative SAP negative

Escalate
therapy of
Functional HB therapy Functional HB
surgery

69
 Indications for pH monitoring

Definite indications Emerging indications

 Typical symptoms (heartburn, regurgitation)
persisting despite PPI therapy
 Monitoring of reflux burden following invasive
 • Atypical symptoms (chest pain, cough, laryngeal
reflux procedures and surgery
symptoms), to confirm or exclude GERD
 • Documentation of abnormal esophageal reflux  • Monitoring of reflux burden following
burden before invasive antireflux procedures and ablation of the LES in achalasia
surgery
 • Diagnosis of functional heartburn and reflux
hypersensitivity (by exclusion of pathological AET)
 • Diagnosis of supragastric belching (pH impedance)
and rumination syndrome (in conjunction with
manometry) 70 Edoardo Savarino Et Al, Nature Reviews - Gastroenterology & Hepatology, 2017
 Indications fro esophageal manometry

Definite Indications for manometry in

GERD Emerging indications
 Localization of the LES for appropriate placement of
pH and pH-impedance catheters
 Assessment of morphology and integrity of the
 • Exclusion of major motor disorders, especially
achalasia esophago-gastric junction
 • Assessment of esophageal peristaltic performance  • Measurement of hiatus hernia size
before invasive antireflux procedures and surgery  • Assessment of esophageal peristaltic performance
 • Diagnosis of rumination syndrome and supra-gastric before bariatric procedures
belching (in conjunction with pH impedance)
 • Evaluation of post-fundoplication dysphagia  AET, acid exposure time; LES, lower esophageal
 • Diagnosis of functional esophageal disorders by sphincter
exclusion of major motor disorders

71
Edoardo Savarino Et Al, Nature Reviews - Gastroenterology & Hepatology, 2017
 Take home message

 GERD and reflux symptoms are very common in GI practice

 Not all the patients do have GERD / NERD
 In the definite GERD patients adequate and timed prescription of PPIs
are recommended
 Modern diagnosis in the indefinite cases mandates the use of diagnostic
tools other that endoscopy
 pH monitoring (+/- impedance) is the main modality in the diagnosis in
these cases
 HRM (manometry), and other testing will be available in the near future
for better phenotyping and managing these patients
72
 Further reading sources

1. Modern diagnosis of GERD: the Lyon Consensus - Gyawali CP, et al. Gut
2018;67:1351–1362
2. Advances in the physiological assessment and diagnosis of GERD -
Edoardo Savarino Et Al, Nature Reviews - Gastroenterology &
Hepatology, 2017

73
Thanks for your attention