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

Scope

• Case Scenarios

• Overview & Definitions

• Diagnostic Approach

– Symptoms

– OGD

• Management Approach

– Medical treatments

– Dietary & lifestyle

– Alternative treatments

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Case Scenarios

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Overview

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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

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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

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Pathophysiology

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ROME Criteria

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ROME II

Rome III Criteria

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Duration: 3 vs 6 mths; can be continuous, intermittent or recurrent

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

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Differential Diagnosis

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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

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Based on studies in patients with dyspepsia evaluated with endoscopy

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

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Drug Induced Dyspepsia

• Acarbose

• Antibiotics

• Bisphosphonates

• Corticosteroids

• Iron

• Metformin

• NSAIDs

• Opiates

• Orlistat

• Potassium chloride

• Theophylline

• Herbs, e.g. garlic, gingko

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Value of Symptoms

• Systemic review to compare primary care physicians, gastroenterologists & computer models in diagnosing organic dyspepsia (as determined by endoscopy)

• 15 studies with 11 366 patients

18 JAMA 2006; 295: 1566-76

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

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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

• Patients with dyspepsia > 2 wks (n=347)

• Provisional diagnosis by GPs & gastreonterologists (GAs)

• OGD within 5 days

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• 45% agreement by GPs & GAs

• Unaided clinical diagnosis by both groups unreliable

• 50% PUD & reflux oesophagitis classified as FD

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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

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Value of Endoscopy 23

• 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

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Findings in Dyspepsia

A. Broad Definition

B. Rome Criteria

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Findings in Dyspepsia

A. Asian studies

B. Western studies

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• 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

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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

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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

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„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

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Management Approach

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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

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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

33 1. Arch Int Med 2011; 171: 1929-36

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

34 1. 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

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

35 1. Clin Gastroenterol Hepatol 2007; 5: 178-85 2. Am J Gastroenterol 2007; 102: 1483-8 3. J Clin Gastroenterol 2008; 42: 134-8

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

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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

37 1. J Gastroenterol 2005; 40: 1036-42 2. Clin Gastroenterol Hepatol 2008; 6: 746-52

Diet & Lifestyle

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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

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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

40 1. 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

• „Food intolerance‟ occur more frequently in FD patients

• Few studies evaluate role of specific foods

• Certain foods may provoke specific dyspeptic symptoms

41 14. Carvalho et al. Dig Dis Sci 2012; 55: 60-5 15. Filipovic et al. Eur J Intern Med 2011; 22: 300-4

Specific Foods

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

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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

43 1. Miwa et al. Neurogastroenterol Motil 2012; 24: 464-71 2. Villoria et al. Am J Gastroenterol 2006; 101: 2552-7

Complementary & Alternative Medicine

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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

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• Xiaoyao San:

– Most studied herbal medicine for FD

– Regulates liver Qi, tonifies spleen & nourishes blood

46 J 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

• 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

47 Evid Based Complement Alternat Med 2012; 2012: 936459

• 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

48 Am J Gastroenterol 2012; 107: 1236-47

Back to Scenarios

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Conclusion

• Functional dyspepsia is common

• Need to tailor diagnostic & management approach for each patient

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Diagnostic Algorithm

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Management Algorithm

Thank You

Questions?