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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

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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 of 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

omeprazole/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 of 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 or 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 overall 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 osteoarthritis, 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 of 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 outpatient/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