2. DEFINITION
One of the most common diagnosis made by primary care physician
and gastroenterologists
The Montreal classification defines GERD as:
“Heartburn symptoms or complications resulting from the reflux of
gastric contents into the oesophagus, up to the oral cavity, and lungs.”
Am. J. Gastroenterol. 101 (2006) 1900.
4. DEFINATION
GERD is further classified into two subgroups:
GERD
NERD ERD
heartburn symptoms but
without endoscopic
evidence of mucosal
erosions
NERD Non-Erosive Reflux Disease
ERD Erosive Reflux Disease
Am. J. Gastroenterol.108 (2013) 308–328
heartburn symptoms
accompanied by objective
evidence of erosions
5. Functional heart burn
Falls under endoscopic negative disease but different from NERD
It is Retrosternal burning discomfort or pain refractory to anti-
secretory therapy without presence of
GERD
Histopathologic abnormality
Motility disorder/structural abnormality
For at least three months with symptoms onset at least six months
prior to the diagnosis.
Nat. Rev. Gastroenterol. Hepatol. 10 (2013) 371–380.
6. Epidemiology
In ambulatory care settings, GERD accounts for 17.5% of all digestive
diseases recorded
GERD has a significant impact on both direct and indirect healthcare costs
A recent systematic review of 16 epidemiological studies found the
prevalence of GERD to be
18.1% − 27.8%in North America
8.8% − 25.9% in Europe
2.5% − 7.8% in East Asia
8.7% to 33.1% in the Middle East
11.6% in Australia
23% in South America
Gut 63 (2014)871–880
7. Clinical manifestation
The cardinal symptoms of GERD are:
Troublesome heartburn
Regurgitation
Heartburn is caused by the contact of refluxed material with the
sensitized or ulcerated esophageal mucosa
Heartburn mostly occurs during the postprandial state
Persistent heartburn causes esophagitis, which manifests as
dysphagia (sole presentation in one third of patients)
Neurogastroenterol. Motil. 29 (2017) e12920.
8. Clinical manifestation
Esophageal/ typical symptoms
Heartburn
Regurgitation
Chest pain/epigastric pain
extra-esophageal/ atypical
symptoms
Cough
Laryngitis
Asthma
Dental erosion syndromes
It is not clear if symptoms of odynophagia, water brash,
hypersalivation and globus sensation are directly related to
GERD
Neurogastroenterol. Motil. 29 (2017) e12920.
9. Pathophysiology and risk factors
Reflux can be both physiologic and pathologic
Physiologic reflux
Mostly occurs during the postprandial state
Transient
Does not occur during sleep
Does not result in reflux symptoms
Gastroenterol. Clin. North Am. 25 (1996) 75.
10. Pathologic reflux
Transient loss of
pressure in the
lower esophageal
sphincter (LES)
Transient loss of
pressure is
diagnosed when
persistent LES
relaxation occurs,
lasting more than
10 s.
Gut 63 (2014) 1185–1193.
11. Risk factors
Diet and lifestyle (smoking, alcohol)
Abdominal obesity
Infiltrative disease (e.g. scleroderma),
Myopathy associated with chronic intestinal pseudo-obstruction
Medications
Surgical damage to the LES
Esophagitis
Obesity accounts for 50–70% of patients with reflux symptoms, and
15% of the obese patients also have hiatus hernia
Surg. Obes. Relat. Dis. 9 (6) (2013) 920–924.
12. Risk factors
Medications that increases chances of reflux disease include:
Anticholinergics
Smooth muscle relaxants such as β-adrenergic agents
Aminophylline
Nitrates
Calcium channel blockers
Phosphodiesterase inhibitors
N. Eng. J. Med. 359 (2008) 16.
13. Complications
The various complications of GERD described in the literature
They are mainly divided into three broad categories:
Esophagitis
Peptic stricture
Barrett’s esophagus
(the last two are consequences of longstanding esophagitis)
14. Complications: Esophagitis
Esophagitis is caused by constant irritation of the mucosal surface of
the esophagus
Loss of the defence mechanisms against injuries caused by acid,
pepsin, and bile
Esophagitis can be observed as a direct visualization in upper
endoscopy and/or at the cellular level
15. Complications: Esophagitis
Los Angeles classification system should be used to describe the
endoscopic appearance
Grade A
One or more mucosal
breaks each ≤5 mm in
length
Grade B
At least one mucosal break
>5 mm long, but not
continuous.
Grade C
At least one mucosal break that
is continuous between the tops
of adjacent mucosal folds, but
which is not circumferential.
Grade D
Mucosal break that involves
at least three-fourths of the
luminal circumference
Gastroenterol S0016-5085 (17) (2017), 35977-2
16. Complications: Peptic stricture
Result from fibrosis, causing luminal constriction during the process
of healing from ulcerative esophagitis
The presence of
Granular or nodular pattern in the distal third of the esophagus is consistent
with reflux esophagitis
Luminal irregularities, which suggests esophagitis
17. Complications: Barrett’s esophagus
Major complications of prolonged reflux esophagitis
Normal Squamous epithelium of distal esophagus is replaced by
metaplastic columnar mucosa
This change predisposes to esophageal adenocarcinoma
18. Complications: Barrett’s esophagus
The American College of Gastroenterology recommends screening
for BE in patients with certain risk factors
Caucasian male age >50 years with current/past history of smoking
Chronic (> 5 years) weekly/more frequent symptoms of heartburn and
regurgitation
Patients with central obesity
Patients with family history of BE or EAC
Neurogastroenterol. Motil. 29 (2017) e12954.
19. Complications: Barrett’s esophagus
Endoscopically BE is diagnosed when there:
Extension of salmon colour mucosa ≥1 cm into the distal esophagus
proximal to GEJ
Histologic presence of intestinal metaplasia with goblet cells
Low grade dysplasia can be treated endoscopically or surveillance
EGD can be performed in one year
High-grade dysplasia should be treated endoscopically
All BE patients should receive Proton Pump Inhibitor (PPI) therapy
20. Diagnosis
When patients present with the typical symptoms of heartburn and
regurgitation, no diagnostic tests are necessary
It is recommended that atrial PPI therapy be initiated with once
daily dosing for at least eight weeks
Resolution of symptoms or response to therapy confirms the
diagnosis of GERD
PPI trial approach, has low sensitivity (78%) and specificity (54%)
26. Wireless, Catheter-Free Esophageal pH
Monitoring
Potential Advantages
Improved patient comfort and acceptance
Continued normal work, activities and diet study
Longer reporting periods possible (48 hours)
Maintain constant probe position relative to SCJ
27. Recent advances in diagnostic testing for GERD
Immunohistochemical markers
Multichannel intraluminal impedance-pH monitoring
Narrow-band imaging
Journal: Expert Review of Gastroenterology & Hepatology
DOI: 10.1080/17474124.2017.1309286
28. Immunohistochemical markers
Proteinase-activated receptor -2 (PAR-2) over-expressed in both
erosive and non-erosive GERD
Interleukin-33, G-protein coupled receptor 84, and triggering
receptor expressed on myeloid cells (TREM)-1
The role of any of the above markers as diagnostic markers in GERD
continues to evolve
29. Multichannel intraluminal impedance-pH
monitoring
Requires an ambulatory monitoring with insertion of the impedance
catheter
Unlike traditional ambulatory pH monitoring, impedance testing can
detect non-acidic reflux
Helps determine the extent of reflux
Attempt to correlate these findings to patients’ symptom
30. Narrow-band imaging
Uses spectral narrow band filter for the visualization of mucosal
patterns and microvasculature
Allows increased contrast for better enhancement to detect changes
in the microvasculature
NBI findings on endoscopy include intrapapillary capillary loop
dilatation, microerosions, and vascularity prominence at the
squamocolumnar junction
31. Endoscopic assessment of mucosal impedance
Allow real time measurement during endoscopy
Mucosal impedance (MI) is an endoscopically placed probe that goes
through the working channel of the endoscope that makes direct
contact with the mucosa to obtain measurements
32. Treatment Goals for GERD
Eliminate symptoms
Heal esophagitis
Manage or prevent complications
Maintain remission
34. Non-pharmacologic intervention
Changes in dietary habits
Avoid consumption of foods which have caffeine or theobromine
Coffee
Chocolate
spicy foods
Highly acidic foods
Citrus fruits
Fatty food
Avoid consumption of alcohol and tobacco
Counselling patients to eliminate these foods from their diets is recommended only in those who obtain
symptomatic relief from doing so
35. Non-pharmacologic intervention
Lifestyle modifications
Elevation of the head of the bed
Lying in the left lateral decubitus position
Avoiding the consumption of meals 2–3 h before bedtime
Wear loosely fitted garments
One of the most important modification is to lose
weight
BMI
by
3.5%
40%
reduction in
the frequency
of GERD
symptoms
Dis. Esophagus29 (2016) 197–204
36. Pharmacologic intervention
Medical management is initiated in patients who have persistent
GERD symptoms despite dietary and lifestyle modifications
The main medical therapies available include:
Antacids
Surface agents and alginates
Histamine receptor antagonists (H2RA)
PPI
37. Novel modalities in management of GERD
Medical Endoscopic Surgical
H2RAs
Lavoltidine
EsophyX LES stimulation system
(EndoStim)
PPI
Reversible PPI
Tenatoprazole
MUSE (Medigus
ultrasonic surgical
endoscope)
PPI combination
Vecan
Secretol (omeprazole+
Lansoprazole)
PPI + Alginate
PCABs (potassium
channel blockers)
Michael FV ; Diagnosis and Treatment of Gastroesophageal Reflux Disease; 2016; springer; London
38. What's new
Histamine Type 2 Receptor Antagonists
H2RAs reduce gastric acid secretion by competitive inhibition of the
interaction between histamine and H2 receptors
H2RAs reduce pepsin and gastric acid volume
Nizatidine
Lafutidine
Lavoltidine (AH234844) (Loxtidine)
39. Reversible PPIs
Reversible gastric PPIs
Research efforts are currently targeted at
obtaining reversible proton pump inhibitors
often referred to as acid pump antagonists
(APAs).
None is marketed
K. S. Jain et al. / Bioorg. Med. Chem. 15 (2007) 1181–1205
40. Potassium-Competitive Acid Blockers (P-CABs)
This class of drugs inhibits gastric H+/K+-ATPase in a K+
competitive but reversible mechanism.
P-CABs do not require prior proton pump activation
P-CABs exhibit an early onset inhibition of acid secretion due to
rapid rise in peak plasma concentration
K. S. Jain et al. / Bioorg. Med. Chem. 15 (2007) 1181–1205
41. P-CABs
Linaprazan (AZD 8065) demonstrated similar efficacy as
esomeprazole in healing and controlling symptoms of GERD patients
with EE
However, the drug did not demonstrate any clinical benefits over
esomeprazole in symptom control of patients with NERD
No clinical data available for
Soraprazan
Revaprazan
K. S. Jain et al. / Bioorg. Med. Chem. 15 (2007) 1181–1205
42. Newer prokinetic
Reveprexide
A recent randomized, double-blind, placebo-controlled, parallel-group phase
IIb in 477 patients with GERD who partially responded to PPI treatment;
demonstrated no difference in percentage of regurgitation-free days among
the three reveprexide arms as compared with placebo
Pumosetrag
Pumosetrag (DDP733) is a partial 5HT3 receptor agonist with
gastrointestinal (GI) prokinetic activities
43. Pregabalin
Pregabalin is a centrally acting modulator of voltage-sensitive
calcium channels.
Pregabalin reduced the development of acid-induced
hypersensitivity in the proximal esophagus at 30 and 90 min after
acid stimulation as compared with placebo
could potentially be used in GERD patients who failed to respond to
an adequate anti-reflux therapy
44. Summary of Novel Compounds under
development that have been discontinued
Michael FV ; Diagnosis and Treatment of Gastroesophageal Reflux Disease; 2016; springer; London
45. Surgery
Surgery is indicated for:
Do not respond to optimal medical therapy
Non-compliant patients,
Patients not willing to continue medical management/ those with medication
side effects
The presence of large hiatal hernia
A high volume reflux
Benign strictures, Barrett’s columnar lined epithelium without evidence of
severe dysplasia, or carcinoma
Curr. Gastroenterol.Rep. 10 (2008) 252–257.
46. Surgery
The most common surgical options available for GERD are:
Nissen fundoplication
laparoscopic Nissen fundoplication
Nissen modification
Belsey Mark IV
Hill Gastropexy
Gastric bypass
Angelchik prosthesis
LINX prosthesis
Endoscopic methods
J. Surg. 97 (2) (2010) 139–140.
47. Advances in surgery: Linx reflux management
system
Consists of a series of titanium beads with a magnetic core
connected with titanium wires to form a ring.
This ring is placed around the lower end of the distal esophagus by
laparoscopy
Helps to augment the lower esophageal sphincter and thus prevent
gastroesophageal reflux
50. Electrical Stimulation
Laparoscopic implantation of electrodes in the lower esophageal
sphincter (EndoStim LES Stimulation System)
The electrodes are placed anteriorly along the esophagus at the GEJ
and the generator is implanted in the abdominal wall.
Decreased distal esophageal acid exposure, improved GERD-HRQL,
and less use of PPI medications at 3 years.
52. Endo-luminal therapies for GERD
Also known as transoral incisionless fundoplication (TIF)
EsophyX
The Stretta
MUSE system
53. EsophyX
Used to restore the angle of His by creating a valve at the
esophagogastric junction (EGJ).
This is achieved by delivering multiple full thickness, nonabsorbable
fasteners at the EGJ.
Since its first use in 2005, about 17,000 TIF procedures have been
done
56. The Stretta system (Mederi Therapeutics, Inc.,
Norwalk, CT)
A balloon-tipped four-needle catheter that delivers radiofrequency
energy into the smooth muscle of the EGJ.
The first published report in 2001 showed promising results
Over the last 17 years this therapeutic modality has markedly
improved and has been used in more than 20,000 patients.
World J Gastroenterol. 2014;20(24):7730–7738
57.
58. MUSE system (Medigus, Israel)
An ultrasonic surgical stapler embedded
within a custom endoscope to perform a transoral fundoplication
Kim HJ, Kwon C-I, Kessler WR, et al. Long-term follow-up results of endoscopic treatment of gastroesophageal reflux disease
with the MUSE™ endoscopicstapling device. Surg Endosc. 2016
