Dilemmas of the I have no conflicts of interest Upper GI Tract to - - PDF document

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Dilemmas of the Upper GI Tract

Jeffrey Fox, MD, MPH UCSF Primary Care Medicine: Update 2013

I have no conflicts of interest to disclose Art Byrne

• 42 yo white overweight male
• Has substernal burning once per week

before he goes to sleep at night for 10 years

• No dysphagia, weight loss, early satiety,

blood in stool, or jaundice

• Responds to self-use of antacids
• Flares of symptoms correlate with stress

What should we recommend?

• A. Anti-reflux behavioral management only
• B. Upper endoscopy
• C. Test for H.pylori and treat if positive
• D. Trial of H2RB + behavioral measures
• E. Trial of PPI + behavioral measures

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Art Byrne questions

• When is it OK to do empiric therapy for his

symptoms without further evaluation?

• What therapy should we choose?
• When do we need to do endoscopy?
• Is it safe to use proton-pump inhibitors

long-term?

• Does stress play a role?

GERD burden (GERDen)

• Very common
• 25% of Americans use antacids/

antisecretory meds ≥3X/mo

• $8 billion/year spent antacids/H2RB/PPI
• Detrimental effects on quality of life found

with symptoms as infrequent as once weekly

Ronkainen et.al. Aliment Pharmacol Ther 2006

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The Gallup Organization, 1988

MONTHLY GERD SYMPTOMS

Locke, Gastroenterol, 1997

WEEKLY GERD SYMPTOMS

Nebel, et.al. Am J Dig Dis, 1976

DAILY GERD SYMPTOMS BARRETT’S ESOPHAGUS

Ronkainen et al, Gastroenterol 2005

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ESOPHAGEAL ADENOCARCINOMA ESOPHAGEAL ADENOCARCINOMA

1 in 20,000

Sharma et.al., Gastroenterol, 2006

Defining GERD

• Symptom pattern – heartburn, regurgitation,

dysphagia – How often is “disease”

• Pathologic lesion – erosive esophagitis

– Combo of symptoms and esophagitis highly specific (97%) vs. pH testing – What about those with the symptoms but without the lesion – “NERD”

• “Gold-standard” – pH monitoring best but

imperfect

Whom should I treat empirically?

• Typical symptoms
• No alarm features
• At least partial relief with OTC measures
• Age <55

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Lifestyle measures

• Raise head of bed
• Don’t eat late; >3 hours between meal and

bedtime

• Avoid fatty foods, caffeine, alcohol, citrus,

tomato, peppermint

• Stop smoking
• Weight loss
• Stop offending meds

Lifestyle measures

• Systematic review of effectiveness of

common measures in reducing symptoms

– Randomized controlled trials: NONE – Retrospective/case-control studies:

• Elevating head of bed – yes
• Sleeping in left lateral decubitus position – yes
• Losing weight – yes (Now USPSTF grade B rec)
• Dietary measures – No (!!)

– Included tobacco/alcohol cessation

Kaltenbach, et.al. Arch Intern Med, 2006

Empiric therapy

• H2RAs (ie H2 blockers)
• “Step-up approach”
• Eliminate symptoms in 50% with BID dosing
• Maintains remission in only about 25% of patients
• Appropriate empiric therapy in setting where cost

difference between H2RA and PPI is large

Empiric therapy

• PPIs
• Effective for symptom relief and esophagitis in

85-90% once-daily dosing

• PPI “test” 83% sensitive compared to pH probe/

esophagitis “gold standard”

• In primary care GERD symptom population,

likelihood ratio of positive PPI test 1.2 (CI 0.9-1.6) for pH-proven GERD relative to negative PPI test

Fass, et.al. Aliment Pharacol Ther, 2000 Aanen, et.al. Aliment Pharacol Ther, 2006

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PPIs: Which one?

• 6 agents (omeprazole, lansoprazole,

pantoprazole, rabeprazole, esomeprazole, and dexlansoprazole) all FDA approved and effective for GERD

• Esomeprazole (Nexium) decreases

number hrs pH held above 4 at standard doses and heals esophagitis in slightly higher % of patients than others

Miner,et al. Am J Gastroenterol, 2003

PPIs: Which one?

• However, NO AGENT SUPERIOR for

symptom relief when agents compared head to head.

HENCE:

• Choose the one on formulary; otherwise,

would choose omeprazole because generic

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PPIs: How long?

• Erosive esophagitis – 8 weeks
• Barrett’s esophagus – lifetime
• GERD symptoms – 4-8 weeks, then stop

to see if strict behavioral measures will be effective

• Many need long-term maintenance

therapy

GERD relapses after cessation of therapy

Sandmark, et.al. Scand J Gastroenterol, 1988

Long-term PPI Safety

• Endocrine

– Serum gastrin elevated – theoretical “trophic” risk in gestation – 1st trimester pregnancy use: no increase in birth defects – Gastric carcinoids in rats, no cancer increase in humans

• Nutritional

– Can lower cobalamine (B12) absorption – Not thought to significantly affect iron homeostasis

Dent, et.al. Gut, 1994 Klinkenburg-Knol, et.al. Ann Int Med, 1994 Pasternak B, et al. NEJM, 2010 Fiocca R et al. Alim Pharmacol Ther 2012

Long-term PPI Safety

• Hip fracture

– Case/control study in UK

Duration Hip fracture

• f therapy

Adjusted OR (CI) 1yr 1.22 (1.15-1.30) 2yr 1.41 (1.28-1.56) 3yr 1.54 (1.37-1.73) 4yr 1.59 (1.39-1.80)

Yang et.al. JAMA 2006

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Long-term PPI Safety

• Hip fracture

– Higher risk for “high dose” (over 1.75 doses per day)

• OR 2.65 for high dose/long term

– Lower risk for H2RB though still statistically significant increased risk. – Cases also were more likely than controls to take: anxiolytics (OR 1.76), antidepressants (2.17), NSAIDs (1.38), antipsychotics (3.34), antiseizure meds (3.42), antiparkinsonian meds (3.83), corticosteroids (2.25), and thyroxine (1.40)

Yang et.al. JAMA 2006

Long-term PPI Safety

• Hip fracture

– Higher risk for “high dose” (over 1.75 doses per day)

• OR 2.65 for high dose/long term

– Lower risk for H2RB though still statistically significant increased risk. – Cases also were more likely than controls to take: anxiolytics (OR 1.76), antidepressants (2.17), NSAIDs (1.38), antipsychotics (3.34), antiseizure meds (3.42), antiparkinsonian meds (3.83), corticosteroids (2.25), and thyroxine (1.40)

Yang et.al. JAMA 2006

2010 FDA warning

Long-term PPI safety

• Nurses health study

– Prospective cohort study – 565,786 person-years follow-up – Hip-fracture risk

• Current PPI users 2/1000 person-years
• Non-users 1.5/1000 p-y

– Attributable risk 1/2000 p-y – Adjusted HR 1.35

• Risk disappears after 2 years cessation
• Smoking appears to be cofactor

1Khalili H, et al. BMJ 2012

Long-term PPI Safety

• Why fractures?

– Theoretically, acid inhibition interferes with calcium absorption in the small intestine – However, PPIs do NOT appear to be associated with osteoporosis or accelerated bone mineral density loss – Confounders? – Osteoclast proton-pump inhibition?

Targownik LF, et al. Gastroenterol, 2010 Targownik LF, et al. Am J Gastroenterol 2012

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Long-term PPI Safety

• Community-acquired infections

– Clostridium difficile: Case/control study in UK1

• For people taking PPIs:

OR 2.9

• For people taking H2RBs:

OR 2.0

– Community acquired pneumonia: meta-analysis of case-control studies2

• OR for CAP 1.36 for PPI relative to controls
• Significant heterogeneity and only modest risk

– Theoretical basis is decrease in gastric acidity may be “permissive” to enteric infection (in Cdiff) and reflux/ microaspiration (CAP)

Dial et.al. JAMA 20051 Johnstone J, et.al. Aliment Pharmacol Ther 20102

Long-term PPI safety

• Hypomagnesemia

– FDA safety alert March 2011: Hypomagnesemia is rare but possible adverse effect from long-term PPI use – Special care in patients also on other meds that can cause hypoMg (eg diuretics, digoxin) – Can result in muscle spasm, seizures, and cardiac events

What about PPIs and Plavix?

• Plavix effect on platelets thought to be

mitigated by PPIs in ex-vivo platelet aggregation studies (P450 CYP2C19)

• Observational data mixed on event rates
• Randomized trial of PPI + plavix vs. plavix

alone (COGENT)

– no difference in cardiac events – PPI/plavix group had 50% bleeding risk

Bhatt, et al. NEJM 2010

Ho PM et al, JAMA 2009 Ray WA et al. Ann Intern Med 2010 Banergee S et al. Am J Cardiol 2011

ACC/AHA/ACG position

• In patients taking clopidogrel+ASA

– 2008 – ACC/AHA/ACG “take PPI co-therapy” – 2009 – FDA BOXED WARNING on

• meprazole/esomeprazole plus clopidogrel

– 2010 – ACC/AHA/ACG position update:

• There may be an important interaction
• In high risk patients for UGI bleed, benefits of PPI

co-therapy outweigh risks

• In average risk patients, case-by-case approach
• Use non-omeprazole/esomeprazole PPIs when on

plavix if PPI is needed/advised

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PPI vs aspirin

• Number needed to harm (NNH) = number
• f people who need to be prescribed

medication to have 1 complication above the level of non-users

– GI hemorrhage on annual basis with aspirin treatment: NNH 247-833 – Hip fracture on annual basis with PPI treatment: NNH 20001

1Khalili H, et al. BMJ 2012

Long-term PPI Safety

Still overall good safety profile

• No randomized data proving harm
• Enough retrospective or non-randomized

prospective evidence of potential harm to be judicious

• Needs further study

Questions raised in a given patient:

• Does my patient need this medication?
• What is the lowest effective dosage for shortest

time necessary?

PPI maintenance: On-demand

• Symptom-driven therapy

– Single-dose (true “on-demand”) – Short course (“intermittent therapy”)

• Controlled by patients, not providers
• PPI on-demand therapy may be most

cost-effective of all maintenance strategies

– Fewer meds, adverse reactions, and OVs – Lower overall healthcare costs

• 2011: FDA lifted PPI fracture warning for

OTC

Gerson, et.al. Am J Gastroenterol, 2000

Other PPI recommendations

• If long-term usage deemed necessary:

– Calcium/Vitamin D supplementation – Weight bearing exercise – Periodically monitor vitamin B12

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Refractory patients

• Standard dosing regimen once-daily not working for

“classic” symptoms after 1 month trial once-daily PPI

• OPTIONS:

– Twice-daily (breakfast/dinner) eg omeprazole 20 BID – Add H2RA for nocturnal acid breakthrough

• Recently shown to be of little benefit, but anecdotally some improve

– Twice-daily double dose (eg omeprazole 40 BID)

• Can be helpful in subset

– Other agents: sucralfate, prokinetics, (treat concomitant gastric emptying disorder), baclofen

Vakil et.al. Aliment Pharmacol Ther, 2006 Leite, et.al. Am J Gastroenterol, 1996

GERD and stress

• Animal model

– Rats subjected to stress have more esophageal mucosal permeability and dilated intercellular spaces relative to controls

• Acid exposure in humans is similar in

stress and non-stress, but perception of acid higher in stress

Farre R et.a. Gut 2007

Non-erosive GERD: NERD!

• “Endoscopy-negative GERD”, “functional heartburn”,

“IBS of the esophagus”

• 50-70% of those with classic GERD symptoms
• Less likely to have abnormal pH study
• Mechanisms

– Hypersensitivity – Disordered motility – Psychological factors

• High correlation with female gender, functional GI

disorders, mood disorders

• Can respond to mix of acid reducing meds,

antidepressants, anxiolytics, psychotherapy

Chey WD, Am J Med, 2004

SSRI and NERD

Viazis N et al. Am J Gastroenterol 2012

• 75 patients with hypersensitive esophagus

(reflux symptoms > 6 mo, refractory to BID PPI, negative endoscopy and pH study) randomized to citalopram 20mg once daily

• r placebo

Citalopram Placebo

Reflux symptoms at 6 months

38.5% 66.7%

P=0.021

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• If GERD-like symptoms but no

better on acid reduction:

• STOP/REDUCE ACID

REDUCTION THERAPY

• TRY SOMETHING ELSE

Meds don’t work: What else?

• Referral to specialist
• Anti-reflux surgery
• Psychological/psychotropic therapy
• Naturopathic/alternative

GERD – alarm symptoms

• Dysphagia
• Odynophagia
• Weight loss
• Bleeding (melena, hematemesis)
• Anemia
• Anorexia
• Nausea/vomiting
• Severe or persistent symptoms despite Rx

The further evaluation…

• Endoscopy
• Ambulatory pH testing/impedence testing
• Esophageal manometry
• Barium esophagram
• Other

– Laryngoscopy – Cardiac stress testing – PFTs – Serum gastrin

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Endoscopy referral for GERD ACP guidelines 2012

• Heartburn plus alarm

symptoms

• Persistent symptoms

despite adequate therapy for 4-8 weeks

• Severe erosive

esophagitis despite 2 months hi-dose PPI

• History of esophageal

stricture with recurrent dysphagia

• Established Barrett’s

esophagus

• Select men > age 50

with additional risk factors (eg obesity, smoking, nocturnal symptoms)

Shaheen N et al. Ann Intern Med 2012

Anti-reflux surgery

• Defect in mechanical barrier to reflux corrected
• Laparoscopic Nissen fundoplication
• Success largely operator dependent
• Best candidates: those with GERD on both

subjective and objective measures

• Poor candidates: poor surgical candidates,

atypical symptoms

• Initial success 90-95% in eliminating sx and

healing esophagus (many studies)

Medical vs. Surgical Rx

• 10-13 year follow-up
• No significant difference

between medical and surgical arms in physical and mental well-being or

• verall satisfaction
• 62% of surgical patients

taking meds for GERD symptoms

• ?increased mortality in

surgical arm

Spechler, et.al. JAMA 2001

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GERD and asthma

• Acid reflux can cause bronchoconstriction
• NIH asthma guidelines recommend

investigating GERD in asthma patients, even without GERD symptoms

• Randomized trial Nexium vs placebo in

asthmatics with no or minimal GERD sx

– No difference between groups in symptoms or PFTs, even those with silent reflux

American Lung Association Asthma Clinical Research Centers, NEJM, 2009

GERD and extraesophageal sx

• Laryngitis, chronic cough, asthma
• USPSTF position:

– Treatment recommended when extraesophageal symptoms accompany typical esophageal symptoms (grade B) – Treatment not recommended in absence of typical esophageal symptoms (grade D)

Kahrilas PJ, et al. Gastroenterol 2008

Remember…

• GERD is chronic disease – meds control

most people’s symptoms to a manageable level (75-80% improvement) but do not eliminate them

– Reassurance is enormous part of job

• Empiric therapy appropriate for

uncomplicated disease; alarm symptoms should warrant GI referral

• PPIs are OK but stop if not helping

Barrett’s esophagus covered in “GI malignancies” talk

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Bill Leeder

• 68 yo male with CAD, severe
• steoarthritis, and depression comes to

your for post-hospitalization visit

• Recent admission for UGI bleed from

gastric ulcer

• Takes baby aspirin, ibuprofen, and zoloft

in addition to newly started omeprazole; he was told to stop some medication but cannot remember which one

Which agent placed him at risk for GI bleeding?

• A. Baby aspirin
• B. Ibuprofen
• C. Zoloft
• D. Baby aspirin and Ibuprofen
• E. All of the above

Medications and UGI bleeding COX-2 inhibitors and GI safety

• Main advantage of COXIBs has been fewer

peptic ulcers and better tolerability than non- selective NSAIDs

– Supported by recent Cochrane Meta-Analysis – Compared to standard NSAIDs, COXIBs had:

• Fewer gastroduodenal ulcers (RR 0.26; CI 0.23-0.3)
• Fewer ulcer complications (RR 0.39; CI 0.31-0.5)
• Fewer withdrawals for GI sx (RR 0.65;CI 0.57-0.73)
• Fewer GI bleed events (upper AND lower)

– Need to weigh higher cardiovascular risk, which appears to be directly correlated to degree of Cox-2 selectivity Rostom A, et.al. Clin Gastroenterol Hepatol 2007

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Ray WA, et.al. Gastroenterol 2007

PPI gastroprotection

• NOT FOR MAJORITY OF PATIENTS
• ACG guidelines 2009

– High risk

• Hx of complicated peptic ulcer disease or
• More than 2 risk factors (below)

– Moderate risk (1-2 risk factors)

• Age >65
• High-dose NSAIDs
• Hx of uncomplicated ulcer disease
• Use of aspirin, corticosteroids, or anticoagulants

– Low risk

• None of the above

SSRIs and UGI bleeding

• Current, recent, or past SSRI use is

associated with a 1.67, 1.88, and 1.22 OR

• f an UGI bleed
• Risk was increased with concurrent use of

NSAIDs or anti-platelet therapy and decreased with concurrent use of PPI

• TCAs did not show this association
• Inhibition of platetet activity possible

mechanism

Dall M, et al. Clin Gastroenterol Hepatol 2009

Low dose aspirin and GIB

• Meta-analysis of dosages 75-325mg/day

RR*

– Decreased overall mortality 0.93 – Increased risk of GI bleeding 1.55 – In combination with aspirin, vs aspirin alone

• Other antiplatelet/anticoagulants

1.86

• PPI

0.34

*All statistically significant Lanas A et al. Clin Gastroenterol Hepatol 2011

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Stopping aspirin after GI bleed?

PPI plus baby aspirin PPI plus placebo Rebleed risk after 8 weeks 10% 5% All-cause mortality after 8 weeks 1% 13%

Patients with peptic ulcer bleed on aspirin Randomized to PPI + aspirin vs. PPI + placebo

Sung, JJY, et.al, Ann Int Med, 2010

Stopping meds after GI bleed

• Within 1 year of GI bleed, many patients

are re-started on the offending medication

SSRIs – 82% NSAIDs – 25% Warfarin – 58% Clopidogrel – 55% – Many patients end up on offending medication plus PPI for gastroprotection

• 20-25% were not

– Poor communication between inpatient and

• utpatient/primary care systems?

Dall M et al. Aliment Pharmacol Ther 2012

http://www.asariskcalculator.com http://www.asariskcalculator.com Lanas A et al. Aliment Pharmacol Ther 2013

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Billie Aiken

• 38 yo black woman comes into your office

with epigastric pain, non-radiating, constant, inconsistently associated with meals for months

• She was born in Haiti but moved to this

country when she was 10

• Denies any blood in stool, early satiety
• She takes no medications
• Only medical problem is IBS

Billie Aiken

• What is the most appropriate initial

approach to her symptoms?

• How likely is she to have H.pylori?
• What is the relevance of the IBS?

Dyspepsia

Pain or discomfort in epigastrium

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Approach to dyspepsia

• Numerous possible initial

approaches

– H.pylori test and treat – Empiric antisecretory (H2RB or PPI) – Endoscopy

Which of the following are not Group 1 (proven) carcinogens:

• A. Human Immunodeficiency Virus (HIV)
• B. Human Papilloma Virus (HPV)
• C. Hepatitis B Virus (HBV)
• D. Helicobacter pylori (H.pylori)
• E. All of the above are considered Group 1

carcinogens

H.pylori: Who has it?

• Prevalence in adults in mid 1990s

– 50% developed world – 80% developing world

• Risk factors

– Lower socioeconomic status – Poor living conditions, eg crowding, lack of running water, housing density

Pounder RE, et.al. Aliment Pharmacol Ther 1995

H.pylori and ethnicity

• NHANES stored sera from 1988-1991

Everhart JE et.al. J Infect Dis 2000 Non-Hispanic White Mexican American African American Prevalence 26.2% 61.6% 52.7% Odds ratio compared to White NA 6.3 (4.8 - 8.3) 3.9 (3.1 - 4.9)

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H.pylori: Declining prevalence

• Within a given country, appears to relate

to improvements in economic status and sanitation

– In Japan, H.pylori seropositivity

• Born prior to 1950: > 70%
• Born 1950-1960:

45%

• Born after 1960:

25% Asaka M, et.al. Gastroenterology 1992

H.pylori associations

• Duodenal and gastric ulcers
• Gastric cancer

– MALT – Gastric adenocarcinoma – Atrophic gastritis/gastric intestinal metaplasia

• Functional dyspepsia

H.pylori and ulcers

• Strong association between H.pylori

and duodenal ulcers, less strong for gastric ulcers

• Synergistic effect with H.pylori and

NSAIDs in ulcer incidence

• Effective eradication of H.pylori clearly

reduces ulcer recurrence

Does H.pylori cause gastric cancer?

• Direct damage to mammalian epithelial

DNA has been shown

• Patients with H.pylori infection have a

higher rate of gastric adenocarcinoma than patients without1

• Treatment of H.pylori in MALT lymphoma

when early stage can be curative

1Toller IM, et. Al. Proc Nat Acad Sci, 2011

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Does eradicating H.pylori reduce risk of cancer?

• Meta-analysis of follow-up from 6

randomized controlled treatment trials

– Mean 4-10 years of follow up – 6,695 patients

Treated Untreated Developed gastric adenocarcinoma 1.1% 1.7% Relative risk of gastric cancer: 0.65 (95% CI 0.43-0.98)

Fuccio L et.al. Ann Intern Med 2009

H.pylori and functional dyspepsia

• Controversial association between

functional dyspepsia (FD) and H.pylori

• Evidence that H.pylori eradication in FD

improves symptoms is mixed

• Meta-analysis shows SMALL but

statistically significant improvement in HP eradication in FD1

– NNT 18 for 1 improvement over placebo

1Moayyedi P, et.al. Cochrane Database Syst Rev 2005

H.pylori testing

• Serology
• Urea breath test
• Stool antigen
• Endoscopic biopsy

– Histology – Culture

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H.pylori testing

• Serology test/treat
• Urea breath test
• Stool antigen
• Endoscopic biopsy

– Histology – Culture

Check eradication or for recurrent symptoms post-eradication

H.pylori testing

• Serology test/treat
• Urea breath test
• Stool antigen
• Endoscopic biopsy

– Histology – Culture

Check eradication or for recurrent symptoms post-eradication

H.pylori testing caveats

• Serology positive for life, does not

separate current from past infection

– Not useful as serial test

• PPIs cause false negative of urea breath

test and stool antigen test

– Must be off PPIs for at least 2 week to avoid false negative results

H.pylori treatment

• First-line therapy (AOC) X 10-14 days1

– Amoxacillin 1000mg BID – Clatrithomycin 500mg BID – PPI standard dose BID

• PCN allergic: Switch Flagyl 500mg BID

for Amoxacillin

• 7 days nearly as effective as 10-14

days2

• Treatment-failures, numerous regimens

1Chey WD, et.al. Am J Gastroenterol 2007 2Fuccio L, et.al. Ann Intern Med 2007

Eradication

80%

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H.pylori sequential vs standard

Sequential

PPI + Amox X 5 days then PPI + Biaxin + Flagyl X 5 days

Standard

PPI + Amox + Biaxin X 14 days

Eradication

(intention to treat)

85.9% 75%

Eradication

(per protocol) 92.6%

85%

• Resistance to

standard “triple therapy” increasing

• Sequential therapy

may improve eradication over standard triple therapy

p = 0.006

Kim YS, et al. Aliment Pharmacol Ther 2011

p=0.019

• H. Pylori and GERD
• Try to distinguish GERD symptoms from

dyspepsia!!

– Often difficult – overlapping and multiple complaints – Poor correlation between patient & clinician symptom assessement (kappa 0.17-0.53) – Treatment of H.pylori may WORSEN GERD

• H.pylori infection in some observational studies

lower in patients with GERD symptoms

• Randomized trial did NOT confirm GERD higher in

H.pylori treated patients

McColl, et.al. Am J Gastroenterol 2005 Moayyedi, et.al. Gastroenterol 2001

Will I miss cancer if no endo?

• 2,741 patients with dyspepsia without

alarm symptoms

– 6 cancers (3 gastric/3 esophageal) (0.2%)

• Only 1 cancer in patient under 50
• Cost per cancer $16,000 - $82,000

– 23.2% had any mucosal findings

Vakil N, et al. Clin Gastroenterol Hepatol 2009

Use of endoscopy in dyspepsia

• Always with alarm symptoms

– Alarm symptoms poor predictor of organic pathology

• Failure to improve despite empiric therapy
• Appropriate age “cut off” is controversial

– Guidelines vary from 45-55 – UGI cancer rare prior to age 55

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How to approach a patient with dyspepsia

Dyspepsia

Endoscopy CBC/LFT/amylase/TTG Consider imaging if WL

All explanations considered? *Med side effect *Biliary source *Cardiac source

Test and treat Address specific findings

• H. pylori likely?

Empiric anti- secretory therapy

Treat functional dyspepsia

Endoscopy

Monitor for recurrent symptoms

Alarm symptoms or age > 55? yes no normal abnormal yes no no yes Symptom resolution? neg findings yes no

Functional dyspepsia

• Pain in epigastrium without identifiable “organic

cause” (endoscopy negative)

• What’s wrong then? Not clear.

– Motility disorder? – Visceral hypersensitivity? – Psychosocial factors? – Altered brain-gut axis?

• Overlap with other functional GI disorders (eg

NERD, IBS)1

• 2/3 of pts presenting with dyspepsia have FD

1Corsetti M et.al. Am J Gastroenterol 2004

Functional dyspepsia: Medical Management

Saad RJ, et.al. Aliment Pharmacol Ther 2006

Therapy NNT

PPI 9 H.pylori eradication 18 Prokinetics 4 (included cisapride) TCA/anxiolytics 4

Anatacids, bismuth, sucralfate No better than placebo

NNT = Number needed to treat = 1/effect size

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Functional dyspepsia: Anything else?

• Psychotherapy

– Individual trials suggest benefit – Systematic review unable to synthesize1

• Studies too diverse
• High dropout rates in control groups
• Complementary alternative medicine2

– STW 5 (Iberogast) – Capsaicin – red chili pepper – Artichoke leaf extract

Soo S et.al. Am J Gastroenterol 20041 Saad RJ et.al. Aliment Pharmacol Ther 20062

Cannabinoid hyperemesis

• Cyclic N/V associated with epigastric pain
• Long-term (>1 year) cannabis use

– At least weekly use, often daily

• Relief with hot showers/baths
• Resolution with cessation of cannabis
• Also supportive but not essential:
• Age under 50
• Weight loss > 5kg
• Morning symptom predominance
• Normal bowel habits
• Negative laboratory, radiographic,

and endoscopic test results

Simonetto DA, et al. Mayo Clin Proc, 2012

Cannabinoid hyperemesis

• Cyclic N/V associated with epigastric pain
• Long-term (>1 year) cannabis use

– At least weekly use, often daily

• Relief with hot showers/baths
• Resolution with cessation of cannabis
• Also supportive but not essential:
• Age under 50
• Weight loss > 5kg
• Morning symptom predominance
• Normal bowel habits
• Negative laboratory, radiographic,

and endoscopic test results

Simonetto DA, et al. Mayo Clin Proc, 2012