Dyspepsia is one of the most common symptoms in the adult population, and affects 20-40% of adults annually. We present an evidence based approach to this common topic, incorporating the latest guidelines.

1. Dyspepsia
An Evidence Based Approach
Asian Consensus 2012, NICE 2014, Rome III 2006, AGA 2005, ACG 2005
Dr Jarrod Lee
gutCARE @ Mount Elizabeth Novena Hospital

2. Scope
• Case Scenarios
• Overview & Definitions
• Diagnostic Approach
– Symptoms
– OGD
• Management Approach
– Medical treatments
– Dietary & lifestyle
– Alternative treatments
2

3. Case
Scenarios
3

4. Overview
4

5. Overview
• Dyspepsia affects 20-40% of adults annually
• 7-40% prevalence based on population studies
• 50% self medicate
• 10-25% will seek medical attention
• Quality of life impaired; more absent work days
• Symptoms often short duration & self limited,
but may be chronic
5

6. Definitions
• Dyspepsia:
– Symptom or set of symptoms considered to originate
from gastroduodenal region
• Symptoms:
– Epigastric pain, epigastric bloating, postprandial
fullness, early satiety, nausea, vomiting, belching
• Functional Dyspepsia:
– Characterized by chronic dyspepsia in absence
organic, systemic or metabolic conditions
– Definition evolved considerably over last 20 yrs
6

7. 7
Pathophysiology

8. 8

9. 9
ROME Criteria

10. 10
ROME
II

11. Rome III Criteria
11
Duration: 3 vs 6 mths; can be continuous, intermittent or recurrent

12. Rome II  III: Paradigm Shift
• From “pain or discomfort in upper abdomen” to
accommodate variations in symptoms & patterns
• Recognizes “meal related” (PDS) & “pain
related‟ (EPS) symptoms associated with distinct
pathophysiological mechanisms
• Syndromes may overlap:
– FD can co-exist with GERD & IBS
– Overlap of EPS & PDS: 15%
– Up to 40% may switch FGID subgroups over 10 yrs
12

13. Differential
Diagnosis
13

14. Differential Diagnosis
Diagnosis Prevalence
Functional dyspepsia Up to 70%
Peptic ulcer disease 15-25%
Reflux oesophagitis 5-15%
Gastric or oesophageal cancer < 2%
Others: abdominal cancer, biliary tract
disease, malabsorption, infilitrative
disease, parasites, gastroparesis,
hepatoma, systemic disease, etc
Rare
14
Based on studies in patients with dyspepsia evaluated with endoscopy

15. Asian Populations
• Different diet, lifestyle, HP prevalence
• Majority of dyspepsia without alarm symptoms
have FD: mainly from single studies
– China (2005): 69%
– Korea (2004): 70%
– Malaysia (2008): 62%
– Singapore (2002): 80%
• Significant overlap with IBS: up to 25%
• May have significant overlap with GERD
15

16. Drug Induced Dyspepsia
• Acarbose
• Antibiotics
• Bisphosphonates
• Corticosteroids
• Iron
• Metformin
• NSAIDs
• Opiates
• Orlistat
• Potassium chloride
• Theophylline
• Herbs, e.g. garlic,
gingko
16

17. 17
Value of
Symptoms

18. • Systemic review to compare primary care physicians,
gastroenterologists & computer models in diagnosing
organic dyspepsia (as determined by endoscopy)
• 15 studies with 11 366 patients
18JAMA 2006; 295: 1566-76

19. Sensitivity Specificity Positive
LR
Negative
LR
Primary Care Physicians
4 studies; n=1459
67-95% 25-52% 1.3 0.66
Gastroenterologists
5 studies; n=3707
59-86% 63-71% 1.9 0.4
Computer Models
9 studies; n=7148
60-99% 17-80% 1.6 0.45
19
Conclusions
• Diagnosis based on clinical history of limited use in
distinguishing organic & functional dyspepsia
• Clinical opinion & computer models better than chance
• Differences between groups not statistically significant

20. • Patients with dyspepsia > 2 wks (n=347)
• Provisional diagnosis by GPs &
gastreonterologists (GAs)
• OGD within 5 days
20

21. • 45% agreement by GPs & GAs
• Unaided clinical diagnosis by both groups unreliable
• 50% PUD & reflux oesophagitis classified as FD
21

22. Alarm Symptoms
• Low PPV for diagnosis of organic causes
• Consensus is to investigate further
• Alarm symptoms:
– Unintended LOW, progressive dysphagia, recurrent or
persistent vomiting, BGIT, anemia, fever, positive FH
• OGD is diagnostic modality of choice
• Selected cases if OGD negative:
– US or CT
– FBC, RP, TFT, LFT, stool for parasites
22

23. Value of Endoscopy 23

24. • 9 studies with dyspepsia & OGD; N=5,389
• OGD findings in patients with dyspepsia
compared to those without dyspepsia
• Only PUD more common in dyspepsia; OR 2.07
24

25. Findings in
Dyspepsia
A. Broad
Definition
B. Rome
Criteria
25

26. Findings in
Dyspepsia
A. Asian
studies
B. Western
studies
26

27. • 5 066 consecutive OGDs for dyspepsia
• 19.5% had significant disease: PUD (14.9%),
oesophagitis (5.0%), cancer (0.5%)
• Cumulative frequency of cancer:
– < 35 yrs: 0.68 per 1000 OGDs
– < 45 yrs: 1.15
– > 45 yrs: 9.60
27

28. Diagnostic Approach
• FD is a diagnosis of exclusion
– Need to focus on excluding serious & specifically
treatable diseases
– Balance against resources needed for investigations
• Consider empirical therapy
– History & physical examination alone has low
sensitivity & specificity for predicting organic disease
– High incidence of normal endoscopy
– Very low incidence of cancer
– Investigations are costly & invasive
28

29. Diagnostic Strategies
• Initial strategies for un-investigated dyspepsia:
– Trial of acid suppression
– Test & treat (for HP)
– Early endoscopy
• Cochrane review (2005)
– In absence of warning signs, test & treat is more
effective & cheaper than early endoscopy
– Initial endoscopy provides a small reduction in risk
of recurrent symptoms
29

30. „Cut Off‟ Age
• Consider OGD in new onset dyspepsia before
diagnosing FD if above „cut off‟ age
• Cut off age depends on gastric cancer
prevalence
– 40 yrs: high risk population e.g. China, Korea, Japan
– 45 yrs: intermediate risk e.g. Singapore, Malaysia,
Hong Khong, Taiwan, Vietnam
– 50 yrs: low risk e.g. India, Thailand, Bangladesh
30

31. Management Approach
31

32. Treatment
• Frustrating for patient & doctors
• Few proven options
• Management should be individualized
– Continued reassurance & support important
– Generally aimed at the presumed underlying aetiology
• Use „IBS approach‟ to address multiple factors:
– Biological factors e.g. post GI infection
– Psychological factors e.g. psychosocial factors
– Social factors e.g. dietary changes
32

33. HP Eradication
• Large population studies show increased incidence of HP
infection in patient with FD
• Significance of association unclear
• HP eradication reduces risk of PUD and gastric cancer
• Most recent Cochrane meta-analysis of 17 RCTs (2006):
significant symptom relief with RRR 10%, NNT 14
• HEROES trial1: large RCT, primary care setting
– HP eradication vs PPI + placebo
– 50% symptom improvement at 1yr: 49% vs 36.5%
– P=0.01, NNT 8
331. Arch Int Med 2011; 171: 1929-36

34. HP Eradication in Asians
• Meta-analysis of 7 Chinese RCTs1: OR 3.61 benefit
• Recent Chinese study using Rome III criteria2:
– Benefit for epigastric pain & epigastric burning: 60.8-
65.7% vs 33.3-31.8%; P<0.05
– No difference for postprandial fullness, early satiety,
nausea, belching
• 2x Singapore RCTs
– CGH (2006)3: 31% complete symptom resolution;
62% global symptom resolution
– NUH (2009)4: 39% symptom resolution if HP
eradicated; 3% if HP persistent
341. Helicobacter 2007; 12: 542-6 2. World J Gastroenterol 2011; 17: 3242-7
3. J Gastroenterol 2006; 41: 647-53 4. Eur J Gastroenterol Hepatol 2009; 21: 417-24

35. Proton Pump Inhibitors (PPIs)
• Meta-analysis of all 7 trials1
– 6 in Western population, 1 from Asian population
– Modest benefit vs placebo: 40.3 vs 32.7%; NNT 14.6
– Benefit confined to „ulcer like‟ or „reflux like‟ dyspepsia
– Only 1 negative result from Asian (HK) study
• Recent HK RCT2: no benefit
• Singapore open label study3: no benefit
• Multiple studies: no benefit of high dose vs
standard dose
351. Clin Gastroenterol Hepatol 2007; 5: 178-85 2. Am J Gastroenterol 2007; 102: 1483-8
3. J Clin Gastroenterol 2008; 42: 134-8

36. Prokinetics
• Simulate GI motility via different mechanisms
• Cochrane meta-analysis (2006):
– 24 RCTs; N=3,178
– Prokinetics superior to placebo: 57% vs 47%
– RRR 33%, NNT 6
– Mainly for domperidone & cisapride
– Limitations due to high degree of heterogenicity,
small sample sizes, publication bias
• New prokinetics: itopride, acotiamide
36

37. Antidepressants & Anxiolytics
• Limited studies, inconsistent results
• Meta-analysis of 13 trials1 (n=1,717):
– FD improved in 11 trials
– Pooled RRR 45%
• SSRIs & SNRIs: only 1 RCT to date showed no benefit2
• Central factors (e.g. psychological factors, sleep
disturbance) may be important determinants of response
• May be useful for FD-IBS overlap
• Psychotherapy: weak & inconsistent evidence
371. J Gastroenterol 2005; 40: 1036-42 2. Clin Gastroenterol Hepatol 2008; 6: 746-52

38. Diet &
Lifestyle
38

39. Dietary Modification
• Experimental studies suggest certain food ingredients
such as chilli, spice & fats may provoke symptoms
• No well controlled study to demonstrate that dietary
exclusion of specific food ingredients is effective in FD
• Trials are conflicting:
– Some show FD patients consume more fat & less
carbohydrate
– Others show no difference in diets
• Eating pattern: FD patients have no difference in number
of meals, eating speed, or inter meal interval
39

40. Spicy Food
• Capsaicin: Active ingredient in hot & spicy foods
– Activates receptors on nociceptive C fibres, inducing
burning sensation & pain
• Ingestion of capsaicin capsules causes greater symptom
severity in FD patients vs controls1,2
• FD patients had moderate pain at a lower dose of
capsaicin vs controls: 0.5mg vs 1.0mg3
• Symptom scores in FD patients reduced by 2.5g red
peppers per day x 5wks vs placebo: 60% vs < 30%4
401. Neurogastroenterol Motil 2008; 20: 125-33 2. Neurogastroenterol Motil 2011; 23: 918-e397
3. Neurogastroenterol Motil 2012 Nov 21 epub 4. Aliment Pharmacol Ther 2002; 16: 1075-82

41. • „Food intolerance‟ occur more frequently in FD patients
• Few studies evaluate role of specific foods
• Certain foods may provoke specific dyspeptic symptoms
4114. Carvalho et al. Dig Dis Sci 2012; 55: 60-5
15. Filipovic et al. Eur J Intern Med 2011; 22: 300-4
Specific Foods

42. Specific Foods
• Rice
– Completely absorbed in SB, producing little gas
– Low allergenicity, low fibre
– Rice based exclusion diet improves IBS symptoms
– No trials for FD
• Fibre
– May worsen symptoms in FD patients
– Effect uncertain, may be due to IBS overlap
• Fat
– Implicated in some studies
42

43. Lifestyle Factors
• Stress & anxiety shown to be independent predictors
• Large survey of 18,000 FD patients meeting Rome III
criteria vs healthy individuals1
– Higher daily stress & stress susceptibility; P<0.01
– Felt sleep insufficient, less exercise
• Exercise may improve intestinal gas transit in bloating2
• Large community based studies show coffee, smoking &
alcohol not risk factors for FD
431. Miwa et al. Neurogastroenterol Motil 2012; 24: 464-71
2. Villoria et al. Am J Gastroenterol 2006; 101: 2552-7

44. Complementary &
Alternative Medicine
44

45. Herbal Therapies
• RCTs showing benefit vs placebo with:
– STW 5: herbal preparation with bitter
candy tuft, matricaria flower, peppermint
leaves, caraway, liquorice root, lemon balm
– Artichoke leaf extract
• Limited data on:
– Peppermint + caraway oil combination
– Banana powder capsules
• Antioxidants: trials show no benefit
45

46. • Xiaoyao San:
– Most studied herbal medicine
for FD
– Regulates liver Qi, tonifies
spleen & nourishes blood
46J Gastroenterol Hepatol 2009; 24: 1320-5
• Meta-analysis of 33 studies: significantly reduced
symptoms compared to prokinetics alone (OR 3.26)
• Quality of studies generally poor

47. • Meta-analysis of 15 RCTs
• Symptom relief:
– LJZT vs prokinetics: OR 1.96
– XSLJZT vs prokinetics: OR 2.63
• No ADR for LJZT & XSLJZT, ADRs reported in prokinetics
• Most studies poor quality
47Evid Based Complement Alternat Med 2012; 2012: 936459

48. • 72 FD patients by Rome III criteria
• Randomized to acupuncture vs sham acupuncture
– Electro acupuncture performed for 30min, 5 times per
week; total duration 4 weeks
• Symptom Index of Dyspepsia (SID): FD symptoms
– SID improvement significantly better in acupuncture
group: 1.912 to 0.880 vs 1.930 to 1.400; P<0.05
48Am J Gastroenterol 2012; 107: 1236-47

49. Back to
Scenarios
49

50. 50
Conclusion
• Functional dyspepsia
is common
• Need to tailor
diagnostic &
management
approach for each
patient

51. 51
Diagnostic Algorithm

52. 52
Management
Algorithm

53. Thank You
Questions?