uib.no

U N I V E R S I T E T E T I B E R G E N

Funksjonell oesophagussykdom

Jan G. Hatlebakk

Med.avd., Gastroseksjonen

Klinisk Institutt 1

Klinisk institutt 1

Legg inn

«Avdeling / enhet» på hver side:

1 Gå til menyen «Sett inn»

2 Velg: Dato og klokkeslett

3 Skriv navn på avdeling eller

enhet i feltet «Bunntekst»

4 Velg «Bruk på alle"

uib.no

Symptom relief in unselected GERD populations

• Symptom relief is unsatisfactory in a proportion of

patients taking PPIs

• GERD patients with a significant symptom load

Gisbert J et al. Eur J Gen Pract 2009;15: 154-60

uib.no

uib.no

uib.no

Man lærer!

• Refluks kan gi symptomer selv om slimhinnen er intakt!

• … og refluks kan være patologisk!

– Endoskopi-Negativ reflukssykdom

– «NERD»

• Andre stimuli kan også gi brystbrann …

– Ballonger

– Kontraksjoner?

– Luftlommer??

uib.no

Brystbrann

• Sensitivitet for GERD ca.70%

• Spesifisitet for GERD er ukjent, men

uib.no

Roma II – III - IV

• Roma II: Funksjonelt alt som ikke er øsofagitt / Barrett

• Roma III: Hvis symptomene korrelerer i tid til refluks, er

det GERD! (eller responderer på PPI!)

• Roma IV: Reflux hypersensitivitet er funksjonelt! (selv

om pasienten responderer på PPI!)

Avdeling / enhet

uib.no

A. Functional Oesophageal Disorders ROME IV

A1. Functional chest pain

A2. Functional heartburn

A3. Reflux hypersensitivity

A4. Globus

A5. Functional dysphagia

uib.no

Brystbrann

• Klassiske symptomer

uib.no

Brystbrann

• Klassiske symptomer

• ENRD

– pH +/-

– SAP +/- ?

– ikke øsofagitt

– økt permeabilitet

• Refluks-øsofagitt

– positive kriterier

?

?

Barretts oesophagus

Funksjonell brystbrann

uib.no

Heartburn normal endoscopy and biopsies

On PPI pH impedance

Off PPI pH monitoring ± impedance

Abnormal acid exposure

Normal acid exposure

Reflux hypersensitivity NERD

Functional

heartburn

GERD Functional heartburn

Reflux

hypersensitivity

Normal acid exposure

Positive symptom reflux association

Abnormal acid exposure

Positive or negative symptom reflux association

Normal acid exposure

Negative symptom reflux association

Negative symptom

reflux association

Positive symptom

reflux association

Unproven GERD Proven GERD

GERD overlap

uib.no

GE refluks

Refluks-

øsofagitt

(RE)

Endoskopi-

negativ

GERD

Hypersensitiv

øsofagus

Funksjonell

brystbrann

(FH)

Funksjonell

dyspepsi

(FD)

C.Jonasson etter Galmiche J-P et al, UEG journal 2013 12

Ikke GERD GERD

Visceral

hypersensitivitet

uib.no

A1. Diagnostic Criteria for Reflux Hypersensitivity

Must include all of the following:

1. Retrosternal symptoms including heartburn and chest pain

2. Normal endoscopy and absence of evidence that eosinophilic esophagitis is the cause of the symptoms

3. Absence of major esophageal motor disorders*

4. Evidence of triggering of symptoms by reflux events despite normal acid exposure on pH or pH-impedance monitoring**

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

* Achalasia, EGJ outflow obstruction, DES, jackhammer, absent peristalsis

** Response to antisecretory therapy does not exclude the diagnosis

uib.no

Acid-sensitive oesophagus

% time pH < 4.0 = 2.3 SAP = 98.5 %

uib.no

pH-måling i spiserøret

uib.no

Impedance–pH Catheter

3cm

5cm

7cm

9cm

15cm

17cm

pH - 5 cm

6 impedance channels

2 pH channels

pH at tip

Adult with Gastric pH

Model ZAN-S62C01E

• pH-måling i ventrikkel og

distale øsofagus

• Impedans-måling i 6 kanaler i

øsofagus

• Symptom Association

Probability (SAP) beregnet

fra begge målinger

Impedans / pH-måling i

oesophagus

uib.no

Refluksepisode, mildt sur

uib.no

SI and SAP

SAP = 100 – p = 100%

SAP 95 – 100% viser økt sensitivitet

uib.no

0

20

40

60

80

100

Study

drug

started

%

4 5 6 7 8 15 1 2 3 Days

Placebo

run-in

PPI test - Sensitivity Proportion with GERD with positive test

Placebo Esomeprazole

20 mg bid

Esomeprazole

40 mg od

uib.no

PPI test - Specificity Proportion without GERD with negative test

Study

drug

started

4 5 6 7 15 1 2 3 Days

Placebo

run-in

0 10 20 30 40 50 60 70

Placebo Esomeprazole

20 mg bid

Esomeprazole

40 mg od

100 %

uib.no

uib.no

A2. Diagnostic Criteria for Functional Chest Pain

Must include all of the following:

1. Midline chest pain or discomfort that is not of burning quality.

2. Absence of evidence that gastro-oesophageal reflux is the cause of the symptom

3. Absence of histopathology-based oesophageal motility disorders

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

uib.no

Høyoppløselig (HR) manometri

uib.no

Chest pain of presumed

oesophageal origin

• 30% of patients with angina-type chest

pain have normal angiograms

• Up to 15% have oesophageal disease

incl. GORD and motility abnormalities

• Others may have functional chest pain

of presumed oesophageal origin

uib.no

Diffuse Oesophageal Spasm

uib.no

Rapid

DES

uib.no

nutcracker

uib.no

jackhammer

uib.no

Central processing of stimuli

Avdeling / enhet

Hoff DAL, NGM 2014

13 patients, 15 healthy controls

No difference in resting EEG or

evoked potentials on oesophageal

electrical stimulation

uib.no

A3. Diagnostic Criteria for Functional Dysphagia

Must include all of the following:

1. Sense of solid and / or liquid foods sticking, lodging, or passing abnormally through the oesophagus

2. Absence of evidence that gastroesophageal reflux is the cause of the symptom

3. Absence of histopathology-based esophageal motility disorders

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

uib.no

Large break

Large break

Breaks in the 20mmHg pressure

3-5cm small break

>5cm major break

Failed if

uib.no

Large break wo/impedance

Flytt rammen opp!

Large break

uib.no

A4. Diagnostic Criteria for Globus

Must include all of the following:

1. Persistent or intermittent, nonpainful sensation of a lump or foreign body in the throat

2.Occurence of the sensation between meals

3.Absence of dysphagia or odynophagia

4. Absence of evidence that gastroesophageal acid reflux is the cause of the symptom

5. Absence of histopathology-based esophageal motility disorders

Criteria fulfilled for the last 3 months with symptom onset at least 6 months prior to diagnosis

uib.no

• The Graduate Hospital: 751 pasienter med

UES manometri over 2.5 år. Pasienter med

UESP

uib.no

Konklusjoner …

• Utredning av funksjonell oesophagussykdom må omfatte

både gastroskopi med biopsi, 24t impedans-pH-måling

og HR manometri

• Reflukssykdom i alle dens former, samt primære

motilitetsforstyrrelser må utelukkes

• Uklar avgrensing mellom patologisk motilitet og uvanlige

motilitetsfunn

• Ofte assosiert med hypersensitivitet for ulike stimuli

• Begrensede terapeutiske muligheter: TCA, SSRI,

calsiumantagonister, pregabalin (Lyrica) …

uib.no

Avdeling / enhet