1. MRGE
Una malattia non solo gastroenterologica?
Marzio Frazzoni
Fisiopatologia Digestiva
Ospedale Baggiovara - Modena

2. GASTROESOPHAGEAL REFLUX
DISEASE (GERD)
Gastroesophageal
reflux occurs when
the pressure
gradient between
the
esophagogastric
junction and the
stomach is lost
Acid




Pepsins
Transient LES
relaxations
accompanied by
reflux
Hypotonic LES
Hiatal hernia
Impaired esophageal
clearance
Bile

3. Definition and classification of GERD
(AGA Guidelines, Gastroenterology, 2008)

4. GERD – The iceberg disease

The prevalence of frequent (at least 2 days per week) typical reflux
symptoms was 23.7% in the adult Loiano-Monghidoro population

The prevalence rates of esophagitis and Barrett’s esophagus in adults
who accepted to undergo EGD were 11.8% and 1.3%, respectively
(Zagari et al, Gut, 2008)
Endoscopy is required for alarm symptoms
(dysphagia, vomiting, anemia, involuntary weight loss)
(AGA Guidelines, 2008)

5. ATYPICAL REFLUX SYNDROMES

Reflux or reflex?

Casual or causal association?

Efficient reflux treatment should improve symptoms

6. Response of NCCP to PPIs in patients
with and without GERD (Kahrilas et al, Gut, 2011)
RR meta-analysis plot of PPI symptomatic response for patients with NCCP
and with (Panel A) and without (Panel B) objective evidence of GERD

7. REFLUX COUGH SYNDROME
(Chang et al, Cochrane Review, 2011)
In adults, there is insufficient evidence to conclude that
GERD treatment with PPIs is beneficial for cough
associated with GERD

8. REFLUX ASTHMA SYNDROME
(Gibson et al, Cochrane Review, 2009)

In asthmatic subjects with GERD, there was no overall improvement in
asthma following PPI treatment for GERD

Subgroups of patients may gain benefit, but it is difficult to predict
responders

9. REFLUX LARYNGITIS SYNDROME
Meta-Analysis Studies

PPI therapy may offer a modest, but non-significant, clinical benefit
over placebo in suspected GERD-related chronic laryngitis (Qadeer
et al, AJG, 2006)

Therapy with a high-dose PPI is no more effective than placebo in
producing symptomatic improvement or resolution of laryngopharyngeal symptoms (Gatta et al, APT, 2007)

10. Posterior laryngitis – a reliable diagnosis?

Concordance among 5 physicians blindly evaluating 120 video
recordings was very low for edema, erythema, as well as likelihood
and severity of laryngopharyngeal reflux (Branski et al,
Laryngoscope, 2002)

Several signs of posterior laryngeal irritation (e.g. interarytenoid bar,
erythema of the median wall of the arytenoids), which are generally
considered signs of laryngopharyngeal reflux, are present in more
than 80% of nonsymptomatic individuals (Milstein et al,
Laryngoscope, 2005)

11. High economic burden of caring for patients
with suspected extraesophageal reflux
(Francis et al, Am J Gastroenterol, 2013)
PPIs
Only 54% of patients improved or resolved over a 5-year period

12. IMPEDANCE-PH MONITORING
REFLUX IS A PHYSICAL EVENT
80
Weakly Alkaline
Refluxes
60
(n) 40
Weakly Acidic
Refluxes
20
Acid Refluxes
0
OFF PPI
ON PPI
PPI transform the vast majority of acid refluxes
into weakly acidic refluxes
(Frazzoni et al, APT, 2009)
Activation of pepsins occurs at pH <4, but proteolytic activity is maintained
up to pH 6 (Pearson & Parikh, APT, 2011)

13. Refractory GERD as diagnosed by impedance-pH
monitoring can be cured by laparoscopic
fundoplication (Frazzoni et al, Surg Endosc, 2013)
A 3-year outcome study
Preoperative ON-PPI findings
Patients (n) (%)
SAP/SI+ for acid refluxes only
4 (11%)
SAP/SI+ for acid and weakly acidic refluxes
4 (11%)
SAP/SI+ for weakly acidic refluxes only
16 (42%)
Abnormal %EAET
6 (16%)
Abnormal number of total refluxes
31 (82%)
No symptom during the study but abnormal
number of total refluxes only
11 (29%)

14. Refractory GERD as diagnosed by impedance-pH
monitoring can be cured by laparoscopic fundoplication
(Frazzoni et al, Surg Endosc, 2013) - A 3-year outcome study
35
300
P = 0.002
30
25
200
20
%EAET
Total
refluxes (n)
15
150
100
10
5
50
0
0
Before surgery
90
ON PPI
After surgery
Before surgery
OFF PPI
200
After surgery
ON PPI
OFF PPI
180
P = 0.011
70
60
50
40
30
20
10
Weakly acidic refluxes (n)
80
Acid refluxes (n)
P = 0.001
250
P = 0.001
160
140
120
100
80
60
40
20
0
0
Before surgery
After surgery
Before surgery
After surgery
 Normal reflux parameters + heartburn/regurgitation remission in 34/38 (89%) patients
Remission of concomitant preoperative NCCP in 4/4 cases and of concomitant preoperative cough in 5/6 cases

15. MRGE
Una malattia non solo gastroenterologica?
TAKE HOME MESSAGES

16. GERD ATIPICA - RACCOMANDAZIONI
(Katz et al, ACG Guidelines, AJG, 2013)

Accurata esclusione delle cause più frequenti di manifestazioni atipiche

La diagnosi di laringite da reflusso non può essere basata sulla sola
laringoscopia

La gastroscopia è indicata solo per sintomi di allarme, non serve per la
diagnosi di GERD atipica

Un PPI trial è indicato solo nei pazienti che riferiscano anche pirosi
retrosternale

Nei pazienti che negano pirosi retrosternale è indicato un test diretto di
reflusso (pH-impedenzometria o pH-metria)

Nei pazienti non responsivi ai PPI sono indicati ulteriori accertamenti

La fundoplicatio laparoscopica non è indicata per il trattamento delle sole
manifestazioni atipiche non responsive ai PPI