9. Prevalenza di pirosi e/o rigurgito acido
nella popolazione di Loiano-Monghidoro
Assenza di pirosi
e/o rigurgito acido
54,7%
Sintomi
quotidiani
2,7%
Settimanali
21,5%
Mensili
21,1%
Zagari R et al, Gut 2008;57;1354-1359
10. Prevalenza di esofagite/NERD o Barrett
(studio Loiano-Monghidoro)
1069 soggetti
Non GERD50,8%
Barrett
0,7%
ERD
11,9%
NERD 36,6%
Zagari R et al, Gut 2008;57;1354-1359
11. Top 10 diagnosi gastroenterologiche in USA
nel 2010
Peery et al, Gastro 2015;149:1731–1741
12. MRGE: cosa è cambiato e cosa bisogna
sapere
• Epidemiologia (alta prevalenza)
• Spettro clinico (molteplici presentazioni cliniche)
• Fisiopatologia (Obesità, tasca acida)
• Diagnosi (pH-impedenzometria, Restech)
• Terapia medica (variabile risposta ai PPI, altre
terapie)
• Terapia endoscopica (ARMS, TIF, MUSE:
meglio aspettare…)
13. Spettro clinico della MRGE-
La classificazione di Montreal
Sindromi
esofagee
Sindromi
extra-
esofagee
15. MRGE: cosa è cambiato e cosa bisogna
sapere
• Epidemiologia (alta prevalenza)
• Spettro clinico (molteplici presentazioni cliniche)
• Fisiopatologia (Obesità, tasca acida)
• Diagnosi (pH-impedenzometria, Restech)
• Terapia medica (variabile risposta ai PPI, altre
terapie)
• Terapia endoscopica (ARMS, TIF, MUSE:
meglio aspettare…)
16. Patogenesi della MRGE
Modello multifattoriale
Fattori aggressivi vs fattori difensivi
SEI
Peristalsi esofagea
Pressione
Lunghezza
Gravità
Produzione
di acidoReflusso
duodeno-gastrico
Svuotamento
gastrico
Resistenza
della mucosa
Saliva
Rilasciamenti
transitori
18. La tasca acida
La tasca acida (acid pocket) è una zona di elevata acidità che si
forma dopo il pasto distalmente alla giunzione gastroesofagea.
Sfintere esofageo inferiore
Tasca acida
Esofago
Reflusso
acido
Contenuto
gastrico
19. pH-metria gastro-esofagea a digiuno e
post-prandiale (nella tasca acida)
Fletcher et al, Gastro 2001;121:775
20. Caratterizzazione dell’acid pocket post-
prandiale mediante pH-metria HR
Kahrilas P et al, Am J Gastroenterol 2013;108:1058
fasting 3 min after meal
43 min after meal17 min after meal
47 min after meal 73 min after meal
24. Meccanismi di RGE nel paziente
sovrappeso/obeso
↑ Esposizione
esofagea acida
↑Rilasciamenti
del LES
Ernia
jatale
↑ Pressione
intragastrica ↑ Gradiente
pressorio GE
↓
Adiponectina
31. pH 4.0pH @ 5 cm
IIM
5 cm
3 cm
7 cm
9 cm
15 cm
17 cm
IIM – pH metria
32. Episodio di reflusso acidoEpisodio di reflusso acido
Estensione prossimaleEstensione prossimale
pH < 4.0 (soglia)
3 cm
5 cm
7 cm
9 cm
15 cm
17 cm
5 cm
IIM – pH metria
33. Episodio di reflusso non-acidoEpisodio di reflusso non-acido
pH < 4.0 (soglia)
Estensione prossimaleEstensione prossimale
3 cm
5 cm
7 cm
9 cm
15 cm
17 cm
5 cm
IIM – pH metria
34. Indicazioni alla Impedenzo+
pHmetria esofagea
• Valutazione del paziente con endoscopia
negativa e sintomi tipici refrattari alla terapia con
PPI, in cui la diagnosi di reflusso non acido può
modificare la terapia
• Valutazione del paziente con sintomi atipici o
dolore toracico refrattari alla terapia con PPI (?)
ACG practice guidelines 2007
Hirano & Richter, AJG 2007;102:668
36. A magnified picture of the Restech® pH
probe showing its downward-oriented shape
and the reference and sensing electrodes.
Ayazi et al, J Gastrointest Surg 2009;13:1422
This sensor detects aerosolized or
liquid acid, resists drying, and does not
require contact with fluid or tissue for
electrical continuity.
38. Parallel pharyngeal pH-metry and
esophageal pH-MII
Hayat et al, J Clin Gastroenterol 2014;48:318
Only 11% of Dx-pH drops to pH<4, 15% pH drops to pH<5, and 10% of pH
drops to pH<5.5 coincided with impedance pH–detected reflux in the
esophageal body
39. MRGE: cosa è cambiato e cosa bisogna
sapere
• Epidemiologia (alta prevalenza)
• Spettro clinico (molteplici presentazioni cliniche)
• Fisiopatologia (Obesità, tasca acida)
• Diagnosi (pH-impedenzometria, Restech)
• Terapia medica (variabile risposta ai PPI, altre
terapie)
• Terapia endoscopica (ARMS, TIF, MUSE:
meglio aspettare…)
40. Guadagno terapeuticoGuadagno terapeutico
Guarigione esofagite
Lieve (gr. A o B)
Severa (gr. C o D)
Scomparsa pirosi
Pazienti con esofagite
Pazienti con NERD
Scomparsa rigurgito
Dolore toracico (50% miglior.)
MRGE + (pH o EGDS)
MRGE – (pH o EGDS)
Raucedine (miglior.)
Tosse cronica (miglior.)
Guarigione esofagite
Lieve (gr. A o B)
Severa (gr. C o D)
Scomparsa pirosi
Pazienti con esofagite
Pazienti con NERD
Scomparsa rigurgito
Dolore toracico (50% miglior.)
MRGE + (pH o EGDS)
MRGE – (pH o EGDS)
Raucedine (miglior.)
Tosse cronica (miglior.)
Efficacia degli IPP nei vari segmenti dello
spettro clinico (dati degli studi clinici)
Kahrilas et al, Gut 2012;61:1501
44. Acido jaluronico (HA) + condroitinsolfato
(CS): un protettore della mucosa esofagea
HA+ CS costituiscono un “device” di classe III, cioè un dispositivo che esercita
il suo effetto favorevole mediante azione meccanica
45. HA+CS HA+CS
Effetto di HA+CS sul miglioramento dei sintomi
in pazienti con MRGE: un RCT cross-over
HA+CS HA+CS
47. Study design and patient sample
+ IPP
dose
piena
IPP
Effetto di HA+CS, come terapia “add-on”, in
pazienti con NERD resistente agli IPP: un RCT
HA+CS
HA+CS
[Savarino et al, submitted]
48. HA+CS
HA+CS
Effetto di HA+CS, come terapia “add-on”, in
pazienti con NERD resistente agli IPP: un RCT
[Savarino et al, submitted]
49. MRGE: cosa è cambiato e cosa bisogna
sapere
• Epidemiologia (alta prevalenza)
• Spettro clinico (molteplici presentazioni cliniche)
• Fisiopatologia (Obesità, tasca acida)
• Diagnosi (pH-impedenzometria, Restech)
• Terapia medica (variabile risposta ai PPI, altre
terapie)
• Terapia endoscopica (ARMS, TIF, MUSE:
meglio aspettare…)
50. Effetto della resezione mucosa anti-
reflusso (ARMS) sulla giunzione GE
Inoue et al, Ann Gastroenterol 2014;27: 346
In tutti i casi trattati (N=10), è stato possibile sospendere gli IPP
senza recidiva sintomatica.
51. Con la TIF si realizza
endoscopicamente una plicatura
sierosa-sierosa che include lo strato
muscolare, e crea una valva di 3–5
cm di lunghezza e 200–300◦ di
circonferenza
Transoral incisionless fundoplication
(TIF) con EsophyX®
54. Efficacia di TIF in pazienti con MRGE
refrattaria (N=63)
Trad et al. BMC Gastroenterology 2014;14:174
Dei 20 pazienti con sintomi da MRGE refrattari agli IPP (6 mesi),
65% (13/20) hanno riportato eliminazione completa di rigurgito e
pirosi dopo TIF (senza IPP); si è ottenuta la guarigione dell’esofagite
in 75% (6/8) dei casi. 71% dei pazienti avevano eliminato la terapia
con IPP a 6 mesi dalla TIF.
Dei 20 pazienti con sintomi da MRGE refrattari agli IPP (6 mesi),
65% (13/20) hanno riportato eliminazione completa di rigurgito e
pirosi dopo TIF (senza IPP); si è ottenuta la guarigione dell’esofagite
in 75% (6/8) dei casi. 71% dei pazienti avevano eliminato la terapia
con IPP a 6 mesi dalla TIF.
57. Zacherl et al, Surg Endosc 2015;29:220
Effetti dell’endofundoplicatio con
MUSE®
Lo studio indica che MUSE
(approvato FDA e CE) può
realizzare un emifundoplicatio
endoscopica anteriore e
rappresentare un’alternativa alla
Nissen laparoscopica in soggetti
con MRGE che vogliano
sospendere/ridurre i PPI.
58. Conclusioni
• Nella MRGE molto è cambiato in questi ultimi 10 anni
• I cambiamenti sono in parte ascrivibili a una modificata
epidemiologia, in parte a evoluzioni tecnologiche, in
parte a una maggiore attenzione verso questa patologia
• E’ difficile prevedere un cambio radicale nella terapia
farmacologica a breve-medio termine (dagli IPP ai P-
CAB?) ma forse sarà possibile approdare anche in
questa patologia, grazie ai Big Data, ad un approccio
personalizzato (cosiddetta Precision Medicine, Systems
Biology, ecc)
Notes de l'éditeur
Da: Approach to the patient with presumed
extraoesophageal GERD. Fehmi Ates, Michael F. Vaezi
Best Practice & Research Clinical Gastroenterology 27 (2013) 415–431
Lo spettro clinico è complesso, comprendendo sintomi tipici, atipici e complicanze sia esofagei che extra.
La diapositiva analizza i singoli fattori difensivi e aggressivi. Il più importante dei primi è sicuramente lo sfintere esofageo inferiore (SEI), la cui competenza può essere considerata da un punto di vista meccanico (lunghezza e tono basale) o funzionale (rilasciamenti transitori o inappropriati).
Quest’ultimo meccansimo è il più importante meccanismo di reflusso tanto nel soggetto normale che nel paziente
La diapositiva dimostra chiaramente come la tasca acida rimanga al di sotto dello sfintere esofageo inferiore e del diaframma nel soggetto sano dopo il pasto, mentre essa risulta intrappolata nel sacco erniario sopra il diaframma nel paziente con MRGE. Il fenomeno della tasca acida è particolarmente frequente nell’ernia iatale.
Background & Aims: Obesity has been associated
with gastroesophageal reflux disease (GERD) and its
complication, but the mechanism is unclear. We evaluated
the association between obesity and function of
lower esophageal sphincter (LOS) in subjects without
GERD. Methods: We prospectively recruited consecutive
obese (BMI &gt;30) patients referred for weight
reduction procedure and age- and sex-matched overweight
(BMI 25–30) and normal weight (BMI &gt;20
and &lt;25) subjects. Exclusion criteria included esophagitis,
reflux symptoms, use of proton pump inhibitor,
hiatus hernia &gt;2 cm, and diabetes mellitus with
microvascular complication. All participants underwent
combined 2-hour postprandial esophageal manometry
and pH monitoring after a standard test
meal followed by 24-hour ambulatory pH monitoring.
Results: Eighty-four subjects (obese, 28; overweight,
28; normal weight, 28) were studied. All 3
groups had comparable mean LOS pressure, LOS
length, and peristaltic function. During the postprandial
period, both obese and overweight groups had
substantial increase in 2-hour rate of transient lower
esophageal sphincter relaxation (TLOSR) (normal
weight: 2.1 1.2 vs overweight: 3.8 1.6 vs obese:
7.3 2.0, P &lt; .001), proportion of TLOSR with acid
reflux (normal weight: 17.6% 22.0% vs overweight
51.8% 22.5% vs obese: 63.5% 21.7%, P &lt; .001), and
gastroesophageal pressure gradient (GOPG) (normal
weight: 4.5 1.2 mm Hg vs overweight: 7.1 1.4 mm
Hg vs obese: 10.0 1.5 mm Hg, P &lt; .001). Using
multiple regression model, BMI (r2: 0.70, B: 0.28, 95%
CI: 0.24–0.33, P &lt; .001) and waist circumference (r2:
0.65, unstandardized regression coefficient [B]: 0.10,
95% CI: 0.08–0.11, P &lt; .001) were significantly correlated
with TLOSR. Conclusions: Obesity is associated
with increased TLOSR and acid reflux during the
postprandial period in subjects without GERD. Abnormal
postprandial LOS function may be an early
event in the pathogenesis of obesity-related GERD.
Background: Obesity has been associated with gastro-oesophageal reflux disease (GERD); however, the
mechanism by which obesity may cause GERD is unclear.
Aim: To examine the association between oesophageal acid exposure and total body or abdominal
anthropometric measures.
Methods: A cross-sectional study of consecutive patients undergoing 24 h pH-metry was conducted.
Standardised measurements of body weight and height as well as waist and hip circumference were
obtained. The association between several parameters of oesophageal acid exposures and anthropometric
measures were examined in univariate and multivariate analyses.
Results: 206 patients (63% women) with a mean age of 51.4 years who were not on acid-suppressing drugs
were enrolled. A body mass index (BMI) of .30 kg/m2 (compared with BMI,25 kg/m2) was associated
with a significant increase in acid reflux episodes, long reflux episodes (.5 min), time with pH,4, and a
calculated summary score. These significant associations have affected total, postprandial, upright and supine
pH measurements. Waist circumference was also associated with oesophageal acid exposure, but was not as
significant or consistent as BMI. When adjusted for waist circumference by including it in the same model, the
association between BMI.30 kg/m2 and measures of oesophageal acid exposure became attenuated for all,
and not significant for some, thus indicating that waist circumference may mediate a large part of the effect of
obesity on oesophageal acid exposure.
Conclusions: Obesity increases the risk of GERD, at least partly, by increasing oesophageal acid exposure.
Waist circumference partly explains the association between obesity and oesophageal acid exposure.
The roles of intragastric pressure (IGP), intraesophageal pressure (IEP), gastroesophageal pressure
gradient (GEPG), and body mass index (BMI) in the pathophysiology of gastroesophageal reflux
disease (GERD) and hiatal hernia (HH) are only partly understood.
METHODS: In total, 149 GERD patients underwent stationary esophageal manometry, 24-h pH-metry, and
endoscopy.
RESULTS: One hundred three patients had HH. Linear regression analysis showed that each kilogram per
square meter of BMI caused a 0.047-kPa increase in inspiratory IGP (95% confidence interval [CI]
0.026–0.067) and a 0.031-kPa increase in inspiratory GEPG (95% CI 0.007–0.055). Each kilogram
per square meter of BMI caused expiratory IGP to increase with 0.043 kPa (95% CI 0.025–0.060)
and expiratory IEP with 0.052 kPa (95% CI 0.027–0.077). Each added year of age caused
inspiratory IEP to decrease by 0.008 kPa (95% CI –0.015–−0.001) and inspiratory GEPG to increase
by 0.008 kPa (95% CI 0.000–0.015). In binary logistic regression analysis, HH was predicted by
inspiratory and expiratory IGP (odds ratio [OR] 2.93 and 2.62, respectively), inspiratory and
expiratory GEPG (OR 3.19 and 2.68, respectively), and BMI (OR 1.72/5 kg/m2). In linear regression
analysis, HH caused an average 5.09% increase in supine acid exposure (95% CI 0.96–9.22) and an
average 3.46% increase in total acid exposure (95% CI 0.82–6.09). Each added year of age caused
an average 0.10% increase in upright acid exposure and a 0.09% increase in total acid exposure
(95% CI 0.00–0.20 and 0.00–0.18).
CONCLUSIONS: BMI predicts IGP, inspiratory GEPG, and expiratory IEP. Age predicts inspiratory IEP and
GEPG. Presence of HH is predicted by IGP, GEPG, and BMI. GEPG is not associated with acid
exposure.
The Dx-pH measurement system (Respiratory Technology
Corp., San Diego, CA) is a sensitive and
minimally invasive device for detection of acid reflux in
the posterior oropharynx.9 It uses a nasopharyngeal
catheter to measure pH in either liquid or aerosolized
droplets.
Patients
with nonerosive reflux disease exhibit impaired esophageal mucosal
integrity, which may underlie enhanced reflux perception. In vitro
topical application of an alginate solution can protect mucosal biopsies
against acid-induced changes in transepithelial electrical resistance
(TER). We aimed to confirm this finding in a second model
using 3D cell cultures and to assess prolonged protection in a biopsy
model. We assessed the protective effect of a topically applied
alginate solution 1 h after application. 3D cell cultures were grown by
using an air-liquid interface and were studied in Ussing chambers. The
apical surface was “protected” with 200 l of either alginate or
viscous control or was unprotected. The tissue was exposed to
pH 3 bile acid solution for 30 min and TER change was calculated.
Distal esophageal mucosal biopsies were taken from 12 patients and
studied in Ussing chambers. The biopsies were coated with either
alginate or viscous control solution. The biopsies were then bathed in
pH 7.4 solution for 1 h. The luminal chamber solution was replaced
with pH 2 solution for 30 min. Percentage changes in TER were
recorded. In five biopsies fluorescein-labeled alginate solution was
used to allow immunohistological localization of the alginate after 1
h. In the cell culture model, alginate solution protected tissue against
acid-induced change in TER. In biopsies, 60 min after protection with
alginate solution, the acidic exposure caused a 8.3 2.2% change
in TER compared with 25.1 4.5% change after protection with
the viscous control (P 0.05). Labeled alginate could be seen coating
the luminal surface in all cases. In vitro, alginate solutions can adhere
to the esophageal mucosa for up to 1 h and exert a topical protectant
effect. Durable topical protectants can be further explored as firstline/
add-on therapies for gastroesophageal reflux disease.
Percentage of baseline transepithelial electrical resistance (TER) of 3D
human esophageal cell culture after 30 min exposure of pH 3 0.5 mM
taurodeoxycholic acid solution after application of protectant.