th FA M I LY M E D I C I N E C O N F E R E N C E 2 0 1 8 A ... · dyspepsia, another shared feature...

Associate Professor Dr. Alex Leow HR

Assoc. Professor of Medicine

Consultant Physician

Consultant Gastroenterologist and Hepatologist

2 1 t h F A M I L Y M E D I C I N E C O N F E R E N C E 2 0 1 8

A Practical Approach to

Managing Dyspepsia

Division of Gastroenterology & Hepatology Department of Medicine University of Malaya Medical Centre

Outlines

• Introduction

• Changing trends of disease

• Pathophysiology

• Approach to Diagnosis

• Treatment

Functional Dyspepsia

• The population prevalence of functional dyspepsia is quite variable across the globe • 10–40% in Western countries

• 5–30% in Asia

Dyspepsia ≠ Functional Dyspepsia

Dyspepsia main causes


• 40% of all adults

• 4% GP consultations

• 10% further investigations

• 10-20% NSAID users


• Health economic data indicate that functional dyspepsia has high direct and indirect costs, specifically driven by the high prevalence of comorbidity

• Both organic dyspepsia and functional dyspepsia have similar economic effects.

Functional Dyspepsia, GERD, IBS

Functional Dyspepsia ROME IV Definition

1. One or more of the following a. Bothersome postprandial fullness

b. Bothersome early satiation

c. Bothersome epigastric pain

d. Bothersome epigastric burning

AND

2. NO evidence of structural disease (including upper endoscopy) that is likely to explain the symptoms.

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

Must fulfil criteria for B1a, PDS and/or B1b, EPS

Stanghellini et al. Gastroenterology 2016

Functional Dyspepsia Location of symptoms

30.5

9.5

5.1

11.9 9.4

9.9

0

5

10

15

20

25

30

35

1989-1990 1999-2000 2009-2010

Pe

rce

nta

ge

Duodenal ulcer

Gastric ulcer

* *

p-value <0.001

Changing patterns of upper GI diseases

AHR Leow, YY Lim, WC Liew, KL Goh. Alimentary pharmacology & therapeutics 2016 Apr;43(7):831-7

2.9

8.5 9.5

0

1

2

3

4

5

6

7

8

9

10

1989-1990 1999-2000 2009-2010

Pe

rce

nta

ge

Erosive oesophagitis

* *

AHR Leow, YY Lim, WC Liew, KL Goh. Alimentary pharmacology & therapeutics 2016 Apr;43(7):831-7

P-value=0.075 P-value<0.001

Changing patterns of upper GI diseases

Psychiatric correlation?

• The high prevalence of psychiatric comorbidity in functional dyspepsia, another shared feature with IBS, has generated the hypothesis of a psychiatric origin of the disease

• Long-term data indicate that this cause– effect correlation could go both ways: anxiety can increase the risk of future and new-onset functional dyspepsia and functional dyspepsia without psychiatric comorbidity at baseline can predict higher anxiety and depression scores at follow-up.

• functional dyspepsia without psychiatric comorbidity at baseline can predict higher anxiety and depression scores at follow-up.

Nature Reviews Disease Primers volume3, Article number: 17081 (2017)

Pathophysiology

Functional Dyspepsia Pathomechanisms

Approach to diagnosis

First Approach to Dyspepsia

• Consider possible causes outside of upper GI tract • Heart

• Lung

• Liver

• Gall bladder

• Pancreas

• Bowel

• Consider drugs and stop if possible • Aspirin, NSAIDs, Calcium antagonists, nitrates, theophylline, steroids

Possible differential diagnoses of functional dyspepsia

• Peptic ulcer disease (with or without infection with Helicobacter pylori)

• Gastro-oesophageal cancer

• Gallstones, sphincter of Oddi dysfunction, biliary dyskinesia or gallbladder cancer

• Drug-induced adverse effects (for example, NSAIDs, iron supplements, calcium antagonists, angiotensin-converting enzyme inhibitors, methylxanthines and glucocorticoids)

• Chronic pancreatitis or pancreatic cancer

• Parasitic infections (for example, Giardia intestinalis (also known as Giardia lamblia), Strongyloides spp. and Anisakis spp.)

• Hepatocellular carcinoma

• Chronic mesenteric ischaemia

• Crohn’s disease

• Infiltrative diseases (for example, eosinophilic gastroenteritis and sarcoidosis) Nature Reviews Disease Primers volume3, Article number: 17081 (2017)

Upper GI malignance

• Upper GI malignancy is extremely rare in patients < 55 year-old presenting with uncomplicated dyspepsia

• When found it is usually late and incurable. (No screening)

• Consequently, concern about missing underlying curable malignancy is not a valid indication for scoping patients <55 year-old presenting with uncomplicated dyspepsia.

Gillen et al. Americal Journal of Gastroenterology 1999

AGA Guidelines on Dyspepsia

Dyspepsia and Endoscopy evaluation

Dyspepsia: Symptoms thought to be originated from gastroduodenum

Un-investigated dyspepsia

Functional dyspepsia

Organic dyspepsia (Ulcer, oesophagitis,

cancer)

Alarm symptoms Risk factors

• Age • NSAIDs intake • Barrett’s risk factors (Long-standing reflux, alcohol, smoking and family history)

ENDOSCOPY, etc

When to refer for dyspepsia in 55+ year old

• Alarm symptoms/signs

• Unexplained and persistent recent-onset of dyspepsia without alarm symptoms • Unexplained means no cause known

• Persistent implies present for a length of time

• Recent-onset implies new-not a recurrent episode

Alarm symptoms • New-onset dyspepsia at >55 years of age

• Overt gastrointestinal bleeding, for example, melena

(dark tarry stools) or haematemesis (vomiting blood)

• Dysphagia (difficulty swallowing), especially if

progressive, or odynophagia (pain when swallowing)

• Persistent vomiting

• Unintentional weight loss

• Family history of gastric or oesophageal cancer

• Palpable abdominal or epigastric mass or abdominal

adenopathy

• Evidence of iron-deficiency anaemia Nature Reviews Disease Primers volume3, Article number: 17081 (2017)

Referral for Endoscopy

• Review medications for possible causes of dyspepsia

• (Calcium antagonists, nitrates, theophyllines, bisphosphonates, corticosteroids and NSAIDs)

Eradicate H.pylori if positive




cancer)

ENDOSCOPY, etc

H.pylori infection

• Helicobacter pylori is an important human pathogen associated with and etiologically related to gastric cancer, mucosa-associated lymphoid tissue lymphoma, and peptic ulcer disease as well as a variety of other conditions.1,2

• Person infected with this organism have a 10 to 20% lifetime risk of developing PUD.3

1.Sugano K, Tack J, Kuipers EJ, et al. Gut. 2015; 64:1353–1367. 2. Graham DY. Gastroenterology. 2015;148:719–731. 3. Miernyk, K. J. Clin. Microbiol. September 2011 vol. 49 no. 9 3114-3121

NNT is 13 (95%CI, 9-19)

Helicobacter pylori prevalence (%) in relation to time

51.7

30.3

11.1

0.0

10.0

20.0

30.0

40.0

50.0

60.0

1989-1990 1999-2000 2009-2010

Pe

rcen

tage

Alex HR Leow et al. Alimentary pharmacology & therapeutics 2016 Apr;43(7):831-7.

Getting more difficult to treat

Graham, Yamaoka Gut 2007 Jul;56(7):1021-3

The eradication rate of H. pylori infection

after standard triple therapy is decreasing

worldwide.

PPI b.i.d., amoxicillin(Ospamox) 1g b.i.d, clarithromycin(Klacid) 500mg b.i.d

bismuth subcitrate(De-Noltab) 240mg b.i.d PPI b.i.d., amoxicillin(Ospmaox) 1g b.i.d. and

clarithromycin(klacid) 500mg b.i.d

PPI b.i.d., amoxicillin(Ospamox) 1g b.i.d, clarithromycin(Klacid) 500mg b.i.d

7-day STT

7-day modified

Quadruple

14-day STT

7 days

7 days

14 days

Alex HR Leow et al. Optimising First Line H.pylori Eradication Therapy:

Prolonging Treatment or Add-on Therapy, Which Is Better? Journal of

Gastroenterology and Hepatology 2015; 30 (Suppl. 4): 7

7-day CLA-TT vs 7-day Bistmuth Quad vs 14-day CLA-TT

7-day CLA-TT vs 7-day Bistmuth Quad vs 14-day CLA-TT

79.3

81.7

88.6

50

55

60

65

70

75

80

85

90

95

100

Erad

icat

ion

rat

e (%

)

p=0.648

p=0.048 odds ratio: 1.48

Eradication rates: Intention-to-treat analysis

7 day STT 95%CI 71.28-85.60

7 day Quad 95%CI 73.80-87.57

14 day STT 95%CI 81.80-93.10

p=0.123

N=364

Alex Hwong-Ruey Leow et al. Optimising First Line H.pylori Eradication Therapy: Prolonging Treatment or Add-

on Therapy, Which Is Better? Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 4): 7

82.8

85.2

91.6

50

55

60

65

70

75

80

85

90

95

100

p=0.610

p=0.042, odd ratio: 1.595

Erad

icat

ion

rat

e (%

)

Eradication rates: Per-protocol Analysis

7 day STT 95%CI 74.87-88.55

7 day Quad 95%CI 77.60-90.56

14 day STT 95%CI 85.22-95.37

p=0.127

7-day CLA-TT vs 7-day Bistmuth Quad vs 14-day CLA-TT N=364

Alex Hwong-Ruey Leow et al. Optimising First Line H.pylori Eradication Therapy: Prolonging Treatment or

Add-on Therapy, Which Is Better? Journal of Gastroenterology and Hepatology 2015; 30 (Suppl. 4): 7

Standard triple therapy for a duration of 7 days can no longer be recommended

European Journal of Gastroenterology & Hepatology 2017, 29:552–559

Varocha Mahachai, Ratha‐korn Vilaichone, Rapat Pittayanon, Jarin Rojborwonwitaya, ..,Alex Leow, Swe Mon Mya, Yi‐Chia Lee, et al. H. pylori Management in ASEAN: the Bangkok Consensus Report. J Gastroenterol Hepatol. 2017 Jul 31.doi: 10.1111/jgh.13911.

In most instances, 14 days therapy is optimal and should be used. Shorter durations are acceptable only if they are proven to reliably achieve the threshold of 95% PP or 90% for ITT.





cancer)

ENDOSCOPY, etc

Postprandial distress syndrome (PDS): Meal-related FD

Epigastric pain syndrome (EPS):

Meal-unrelated FD



Epigastric pain syndrome (EPS): Meal-unrelated FD

Stanghellini et al. Gastroenterology 2016

• Early satiation

• Postprandial fullness

• Other postprandial symptoms

• Epigastric pain

• Epigastric burning

Treatment with proton pump inhibitor

Treatment with prokinetic therapy





cancer)

ENDOSCOPY, etc



Meal-unrelated FD

Prokinetic Acid suppressive

Antidepressants in functional dyspepsia





cancer)

ENDOSCOPY, etc



Meal-unrelated FD


Antidepressant if refractory Psychotherapy

Dietary management

• Report that meal ingestion induces their typical symptoms, and dietary factors are increasingly recognized to play an important part in the generation of symptoms in functional dyspepsia.

Psychotherapy





cancer)

ENDOSCOPY, etc



Meal-unrelated FD


Antidepressant if refractory Psychotherapy

Standard of care

Disease counselling by pharmacist

Fun

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Dys

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psi

a

Ind

ex

Qu

est

ion

nai

re

Follo

w u

p &

Q

ue

stio

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aire

Follo

w u

p &

Q

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stio

nn

aire

Randomise study looking at knowledge empowerment

1 month 3 months

Ongoing study at University of Malaya Medical Centre Division of Gastroenterology & Hepatology Department of Medicine University of Malaya Medical Centre

Sym

pto

ms

QO

L

FD

Recognising &

addressing the disease

H.pylori

Life style

Drugs

Food

Smoking

Pharmacological Intervention Reassurance or Lifestyle

changes

Referral to Gastroenterologist

Stanghellini, V. et al. Gastroduodenal disorder Gastroenterology 150, 1380–1392 (2016).

Conclusions

• Identifying alarming symptoms among patient with dyspepsia is crucial.

• Differentiating symptoms of functional dyspepsia is vital in optimising care.

• Treat H.pylori infection

• Recommended H.pylori regimen in Malaysia is 14-day Clarithromycin based triple therapy.

• Treat post-prandial distress syndrome with prokinetics

• Use acid suppression in epigastric pain syndrome

• Consider antidepressant in refractory epigastric pain syndrome patient.

Conclusions

• Ultimately, counselling and knowledge empowerment is important in improving patients’ quality of life.

Medicine treat diseases but it is doctor's heart that healed patients.

Presented by:

Vision of Excellence in Digestive Disorders & Sciences

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